471 results on '"Pei, Xuetao"'
Search Results
152. Genetic Modification of Embryonic Stem Cells with VEGF Enhances Cell Survival and Improves Cardiac Function
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Xie, Xiaoyan, primary, Cao, Feng, additional, Sheikh, Ahmad Y., additional, Li, Zongjin, additional, Connolly, Andrew J., additional, Pei, Xuetao, additional, Li, Ren-Ke, additional, Robbins, Robert C., additional, and Wu, Joseph C., additional
- Published
- 2007
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153. RhoGTPases in stem cells
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Yao, HaiLei, primary, Xie, XiaoYan, additional, Wang, DongMei, additional, and Pei, XueTao, additional
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- 2007
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154. Therapeutic applications of bone marrow-derived stem cells in liver transplantation for end-stage liver diseases
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Luo, HaiYing, primary, Wang, YunFang, additional, Kong, Wei, additional, and Pei, XueTao, additional
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- 2007
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155. Generation of insulin‐producing cells from PDX‐1 gene‐modified human mesenchymal stem cells
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Li, Yanhua, primary, Zhang, Rui, additional, Qiao, Haifa, additional, Zhang, Heping, additional, Wang, Yunfang, additional, Yuan, Hongfeng, additional, Liu, Qinbin, additional, Liu, Daqing, additional, Chen, Lin, additional, and Pei, Xuetao, additional
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- 2007
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156. Structure of Human Spindlin1
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Zhao, Qiang, primary, Qin, Lipeng, additional, Jiang, Fuguo, additional, Wu, Beili, additional, Yue, Wen, additional, Xu, Feng, additional, Rong, Zhili, additional, Yuan, Hongfeng, additional, Xie, Xiaoyan, additional, Gao, Yanhong, additional, Bai, Cixian, additional, Bartlam, Mark, additional, Pei, Xuetao, additional, and Rao, Zihe, additional
- Published
- 2007
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157. Expression, Purification, Crystallization and Preliminary X-Ray Analysis of Human Spindlin1, an Ovarian Cancer-Related Protein
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Jiang, Fuguo, primary, Zhao, Qiang, additional, Qin, Lipeng, additional, Pang, Hai, additional, Pei, Xuetao, additional, and Rao, Zihe, additional
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- 2006
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158. Spindlin1, a novel nuclear protein with a role in the transformation of NIH3T3 cells
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Gao, Yanhong, primary, Yue, Wen, additional, Zhang, Peng, additional, Li, Li, additional, Xie, Xiaoyan, additional, Yuan, Hongfeng, additional, Chen, Lin, additional, Liu, Daqing, additional, Yan, Fang, additional, and Pei, Xuetao, additional
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- 2005
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159. Radioprotective effect of FLT3 ligand expression regulated by Egr-1 regulated element on radiation injury of SCID mice
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Du, Nan, primary, Feng, Kai, additional, Luo, Chengji, additional, Li, Liang, additional, Bai, Cixian, additional, and Pei, Xuetao, additional
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- 2003
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160. The role of Hath6, a newly identified shear-stress-responsive transcription factor, in endothelial cell differentiation and function.
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Fang Fang, Wasserman, Scott M., Torres-Vazquez, Jesus, Weinstein, Brant, Cao, Feng, Zongjin Li, Wilson, Kitchener D., Wen Yue, Wu, Joseph C., Xiaoyan Xie, and Pei, Xuetao
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TRANSCRIPTION factors ,CELL differentiation ,CELL physiology ,EMBRYONIC stem cells ,GENE expression ,ENDOTHELIAL cells ,SHEARING force - Abstract
The key regulators of endothelial differentiation that is induced by shear stress are mostly unclear. Human atonal homolog 6 (Hath6 or ATOH8) is an endothelial-selective and shear-stress-responsive transcription factor. In this study, we sought to elucidate the role of Hath6 in the endothelial specification of embryonic stem cells. In a stepwise human embryonic stem cell to endothelial cell (hESC-EC) induction system, Hath6 mRNA was upregulated synchronously with endothelial determination. Subsequently, gain-of-function and lossof- function studies of Hath6 were performed using the hESC-EC induction model and endothelial cell lines. The overexpression of Hath6, which mimics shear stress treatment, resulted in an increased CD452CD31+KDR+ population, a higher tubular-structure-formation capacity and increased endothelial-specific gene expression. By contrast, the knockdown of Hath6 mRNA markedly decreased endothelial differentiation. Hath6 also facilitated the maturation of endothelial cells in terms of endothelial gene expression, tubularstructure formation and cell migration. We further demonstrated that the gene encoding eNOS is a direct target of Hath6 through a reporter system assay and western blot analysis, and that the inhibition of eNOS diminishes hESC-EC differentiation. These results suggest that eNOS plays a key role in linking Hath6 to the endothelial phenotype. Further in situ hybridization studies in zebrafish and mouse embryos indicated that homologs of Hath6 are involved in vasculogenesis and angiogenesis. This study provides the first confirmation of the positive impact of Hath6 on human embryonic endothelial differentiation and function. Moreover, we present a potential signaling pathway through which shear stress stimulates endothelial differentiation. [ABSTRACT FROM AUTHOR]
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- 2014
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161. Bone marrow purging with dibutyl phthalate—Experimental basis and a preliminary clinical application
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Wu, Chutse, primary, Yang, Ke, additional, Pei, Xuetao, additional, Tang, Aiping, additional, Wang, Fusheng, additional, and Wang, Lisheng, additional
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- 1995
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162. Induction of umbilical cord blood-derived β2m−c-Met+ cells into hepatocyte-like cells by coculture with CFSC/HGF cells.
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Wang, Yunfang, Nan, Xue, Li, Yanhua, Zhang, Rui, Yue, Wen, Yan, Fang, and Pei, Xuetao
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- 2005
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163. Differentiation of bone marrow derived Thy-1+β2M- cells into hepatocytes induced by coculture with transgenic CFSCs.
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Wang Yunfang, Nan Xue, Zhang Rui, Li Yanhua, Yue Wen, Yan Fang, and Pei Xuetao
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STEM cells ,BONE marrow ,CELL differentiation ,LIVER cells ,INDOCYANINE green ,LIVER diseases ,RATS ,TRANSPLANTATION of organs, tissues, etc. - Abstract
Studies of transplantation in vivo indicted that bone marrow derived stem cells had a potential to differentiate into mature hepatocytes. However, there are lots of doubts and uncertainties in the influencing factors and control agents of effectively inducing stem cell differentiation in vitro, the efficiency of stem cells' differentiation into hepatocytes and differentiated cells' life-span and functional state, etc. In this study, rat bone marrow derived Thy-l
+ β2 M- cells (BDTCs) were induced to differentiate into hepatocytes by co-culturing with CFSC/HGF feeder layers which expressed hHGF efficiently and stably. RT-PCR and immunofluorescent texts proved induced BDTCs expressed infant and adult hepatocyte specific genes. Further more, these cells displayed functions of indocyanine green (ICG) uptake, ammonium metabolism and albumin production. It was shown that growth factors together with hepatic nonparenchyma cells provided a feasible microenvironment for differentiation of bone marrow stem cells into hepatocytes. The studies not only provided a significant biological model for going deep into the mechanism of stem cell plasticity, but also offered a theoretical and technical foundation of gene and stem cell engineering-based regenerative medicine for end-stage liver diseases. [ABSTRACT FROM AUTHOR]- Published
- 2004
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164. miR-1915-3p regulates megakaryocytic and erythroid differentiation by targeting SOCS4.
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Yuan, Xin, Liu, Pengcong, Xu, Lei, Liang, Liqing, Dong, Qian, Fan, Tao, Yue, Wen, Qu, Mingyi, Pei, Xuetao, and Xie, Xiaoyan
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SMALL interfering RNA , *FLOW cytometry , *RESEARCH funding , *PLATELET count , *T-test (Statistics) , *MICRORNA , *PLASMIDS , *CELLULAR signal transduction , *HEMATOPOIESIS , *BLOOD platelets , *ANTIGENS , *BIOINFORMATICS , *GENE expression profiling , *WESTERN immunoblotting , *ONE-way analysis of variance , *HEMATOPOIETIC stem cells , *CELL differentiation , *CYTOKINES , *BIOMARKERS - Abstract
Background: Proper control of the lineage bias of megakaryocytic and erythroid progenitor cells (MEPs) is of significant importance, the disorder of which will lead to abnormalities in the number and function of platelets and erythrocytes. Unfortunately, the signaling pathways regulating MEP differentiation largely remain to be elucidated. This study aimed to analyze the role and the underlying molecular mechanism of miR-1915-3p in megakaryocytic and erythroid differentiation. Methods: We utilized miRNA mimics and miRNA sponge to alter the expression of miR-1915-3p in megakaryocytic and/or erythroid potential cells; siRNA and overexpression plasmid to change the expression of SOCS4, a potential target of miR-1915-3p. The expression of relevant surface markers was detected by flow cytometry. We scanned for miR-1915-3p target genes by mRNA expression profiling and bioinformatic analysis, and confirmed the targeting by dual-luciferase reporter assay, western blot and gain- and lost-of-function studies. One-way ANOVA and t-test were used to analyze the statistical significance. Results: In this study, overexpression or knockdown of miR-1915-3p inhibited or promoted erythroid differentiation, respectively. Accordingly, we scanned for miR-1915-3p target genes and confirmed that SOCS4 is one of the direct targets of miR-1915-3p. An attentive examination of the endogenous expression of SOCS4 during megakaryocytic and erythroid differentiation suggested the involvement of SOCS4 in erythroid/megakaryocytic lineage determination. SOCS4 knockdown lessened erythroid surface markers expression, as well as improved megakaryocytic differentiation, similar to the effects of miR-1915-3p overexpression. While SOCS4 overexpression resulted in reversed effects. SOCS4 overexpression in miR-1915-3p upregulated cells rescued the effect of miR-1915-3p. Conclusions: miR-1915-3p acts as a negative regulator of erythropoiesis, and positively in thrombopoiesis. SOCS4 is one of the key mediators of miR-1915-3p during the differentiation of MEPs. [ABSTRACT FROM AUTHOR]
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- 2024
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165. Decoding human in vitro terminal erythropoiesis originating from umbilical cord blood mononuclear cells and pluripotent stem cells.
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Wang, Xiaoling, Zhang, Wei, Zhao, Siqi, Yan, Hao, Xin, Zijuan, Cui, Tiantian, Zang, Ruge, Zhao, Lingping, Wang, Haiyang, Zhou, Junnian, Li, Xuan, Yue, Wen, Xi, Jiafei, Zhang, Zhaojun, Fang, Xiangdong, and Pei, Xuetao
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CORD blood , *FETAL hemoglobin , *PLURIPOTENT stem cells , *BLOOD cells , *ERYTHROPOIESIS , *GLOBIN genes , *ERYTHROCYTES , *ERYTHROCYTE membranes - Abstract
Ex vivo red blood cell (RBC) production generates unsatisfactory erythroid cells. A deep exploration into terminally differentiated cells is required to understand the impairments for RBC generation and the underlying mechanisms. Here, we mapped an atlas of terminally differentiated cells from umbilical cord blood mononuclear cells (UCBMN) and pluripotent stem cells (PSC) and observed their dynamic regulation of erythropoiesis at single‐cell resolution. Interestingly, we detected a few progenitor cells and non‐erythroid cells from both origins. In PSC‐derived erythropoiesis (PSCE), the expression of haemoglobin switch regulators (BCL11A and ZBTB7A) were significantly absent, which could be the restraint for its adult globin expression. We also found that PSCE were less active in stress erythropoiesis than in UCBMN‐derived erythropoiesis (UCBE), and explored an agonist of stress erythropoiesis gene, TRIB3, could enhance the expression of adult globin in PSCE. Compared with UCBE, there was a lower expression of epigenetic‐related proteins (e.g., CASPASE 3 and UBE2O) and transcription factors (e.g., FOXO3 and TAL1) in PSCE, which might restrict PSCE's enucleation. Moreover, we characterized a subpopulation with high proliferation capacity marked by CD99high in colony‐forming unit‐erythroid cells. Inhibition of CD99 reduced the proliferation of PSC‐derived cells and facilitated erythroid maturation. Furthermore, CD99–CD99 mediated the interaction between macrophages and erythroid cells, illustrating a mechanism by which macrophages participate in erythropoiesis. This study provided a reference for improving ex vivo RBC generation. [ABSTRACT FROM AUTHOR]
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- 2024
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166. Epigenetic regulation of the Wnt signaling inhibitor DACT2in human hepatocellular carcinoma
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Zhang, Xiaomei, Yang, Yunsheng, Liu, Xuefeng, Herman, James G., Brock, Malcolm V., Licchesi, Julien D.F., Yue, Wen, Pei, Xuetao, and Guo, Mingzhou
- Abstract
DACT2(Dapper, Dishevelled-associated antagonist of β-catenin homolog 2) is a member of the DACTfamily involved in the regulation of embryonic development. Human DACT2is localized on 6q27, a region of frequent loss of heterozygosity in human cancers. However, the regulation of DACT2expression and function in hepatocellular carcinoma (HCC) remains unclear. In this study, genetic and epigenetic changes of DACT2were analyzed in HCC cell lines and primary cancer. We found no single-nucleotide polymorphism (SNP) associated with HCC. Promoter region methylation was correlated with loss or reduction of DACT2expression, and restoration of DACT2expression was induced by 5-aza-2’-deoxycytidine (5-AZA) in HCC cell lines. Promoter region methylation was found in 54.84% of primary HCC. Reduction of DACT2expression was associated with promoter hypermethylation, and expression of DACT2was inversely related to β-catenin expression in primary HCC. DACT2suppressed cell proliferation, induced G2-M arrest in cell lines and inhibited tumor growth in xenograft nude mice. The transcriptional activity of TCF-4and the expression of Wnt signaling downstream genes were suppressed by DACT2re-expression and reactivated by depletion of DACT2. In conclusion, DACT2is frequently methylated in HCC and its expression is regulated by promoter hypermethylation. DACT2suppresses HCC by inhibiting Wnt signaling in human HCC.
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- 2013
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167. Research status and prospect of stem cells in the treatment of diabetes mellitus
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Liu, XiaoFang, Wang, YunFang, Li, YaLi, and Pei, XueTao
- Abstract
Beta cell mass and function are decreased to varying degrees in diabetes. Islet cell replacement or regenerative therapy may offer great therapeutic promise to people with diabetes. In addition to primary pancreatic β cells, recent studies on regeneration of functional insulin producing cells (IPCs) revealed that several alternative cell sources, including embryonic stem cells, induced pluripotent stem cells and adult stem cells, can generate IPCs by differentiation, reprogramming, and trans-differentiation. In this review, we discuss stem cells as a potential alternative cell source for the treatment of diabetes.
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- 2013
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168. Advances in cell lineage reprogramming
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Zhou, JunNian, Yue, Wen, and Pei, XueTao
- Abstract
As a milestone breakthrough of stem cell and regenerative medicine in recent years, somatic cell reprogramming has opened up new applications of regenerative medicine by breaking through the ethical shackles of embryonic stem cells. However, induced pluripotent stem (iPS) cells are prepared with a complicated protocol that results in a low reprogramming rate. To obtain differentiated target cells, iPS cells and embryonic stem cells still need to be induced using step-by-step procedures. The safety of induced target cells from iPS cells is currently a further concerning matter. More broadly conceived is lineage reprogramming that has been investigated since 1987. Adult stem cell plasticity, which triggered interest in stem cell research at the end of the last century, can also be included in the scope of lineage reprogramming. With the promotion of iPS cell research, lineage reprogramming is now considered as one of the most promising fields in regenerative medicine, will hopefully lead to customized, personalized therapeutic options for patients in the future.
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- 2013
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169. Hepatogenesis of Adipose-Derived Stem Cells on Poly-Lactide-co-Glycolide Scaffolds: In Vitroand In VivoStudies
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Wang, Min, Pei, Haiyun, Zhang, Lei, Guan, Lidong, Zhang, Rui, Jia, Yi, Li, Baowei, Yue, Wen, Wang, Yunfang, and Pei, Xuetao
- Abstract
Human adipose-derived stem cells (hASCs) have been shown to be multipotent and could be induced into various cell types, which make them the ideal cell source for cell therapy or tissue engineering. However, differentiation of ASCs into hepatocytes on three-dimensional scaffold, an important part of tissue engineering, has not been reported. In this study, to investigate the hepatogenesis of ASCs on porous poly-lactide-co-glycolide (PLGA) scaffolds, we loaded hASCs on these scaffolds. The cell–scaffold complex was implanted into the peritoneal cavity of 70% hepatectomized rats with or without 14 days of induction in hepatic inducing medium. Our results indicated that hASCs cultured on the PLGA scaffolds in the hepatic inducing medium proliferated more efficiently and could be induced into cells with hepatocyte-like phenotypic and functional properties. In vivostudies showed that induced hASCs on PLGA scaffolds survived and maintained hepatic phenotype and function for at least 14 days after implantation; moreover, noninduced hASCs on PLGA scaffolds expressed human albumin 14 days after transplantation. Collectively, these results suggest that porous PLGA scaffolds are suitable for the hepatogenesis of hASCs. These findings might be helpful in the application of hASC-based tissue engineering for liver disease therapy.
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- 2010
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170. Enhanced differentiation of human pluripotent stem cells into pancreatic endocrine cells in 3D culture by inhibition of focal adhesion kinase.
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Liu, Xiaofang, Qin, Jinhua, Chang, Mingyang, Wang, Shuyong, Li, Yali, Pei, Xuetao, and Wang, Yunfang
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FOCAL adhesion kinase ,ENTEROENDOCRINE cells ,HUMAN stem cells ,PLURIPOTENT stem cells ,HUMAN embryonic stem cells ,CELL culture ,GTPASE-activating protein - Abstract
Background: Generation of insulin-producing cells from human pluripotent stem cells (hPSCs) in vitro would be useful for drug discovery and cell therapy in diabetes. Three-dimensional (3D) culture is important for the acquisition of mature insulin-producing cells from hPSCs, but the mechanism by which it promotes β cell maturation is poorly understood. Methods: We established a stepwise method to induce high-efficiency differentiation of human embryonic stem cells (hESCs) into mature monohormonal pancreatic endocrine cells (PECs), with the last maturation stage in 3D culture. To comprehensively compare two-dimensional (2D) and 3D cultures, we examined gene expression, pancreas-specific markers, and functional characteristics in 2D culture-induced PECs and 3D culture-induced PECs. The mechanisms were considered from the perspectives of cell–cell and cell–extracellular matrix interactions which are fundamentally different between 2D and 3D cultures. Results: The expression of the pancreatic endocrine-specific transcription factors PDX1, NKX6.1, NGN3, ISL1, and PAX6 and the hormones INS, GCG, and SST was significantly increased in 3D culture-induced PECs. 3D culture yielded monohormonal endocrine cells, while 2D culture-induced PECs co-expressed INS and GCG or INS and SST or even expressed all three hormones. We found that focal adhesion kinase (FAK) phosphorylation was significantly downregulated in 3D culture-induced PECs, and treatment with the selective FAK inhibitor PF-228 improved the expression of β cell-specific transcription factors in 2D culture-induced PECs. We further demonstrated that 3D culture may promote endocrine commitment by limiting FAK-dependent activation of the SMAD2/3 pathway. Moreover, the expression of the gap junction protein Connexin 36 was much higher in 3D culture-induced PECs than in 2D culture-induced PECs, and inhibition of the FAK pathway in 2D culture increased Connexin 36 expression. Conclusion: We developed a strategy to induce differentiation of monohormonal mature PECs from hPSCs and found limited FAK-dependent activation of the SMAD2/3 pathway and unregulated expression of Connexin 36 in 3D culture-induced PECs. This study has important implications for the generation of mature, functional β cells for drug discovery and cell transplantation therapy for diabetes and sheds new light on the signaling events that regulate endocrine specification. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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171. Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p.
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Qu, Mingyi, Zou, Xiaojing, Fang, Fang, Wang, Shouye, Xu, Lei, Zeng, Quan, Fan, Zeng, Chen, Lin, Yue, Wen, Xie, Xiaoyan, and Pei, Xuetao
- Subjects
PROGENITOR cells ,BONE density ,BLOOD platelet activation ,THROMBOTIC thrombocytopenic purpura ,BONE marrow - Abstract
Thrombosis leads to platelet activation and subsequent degradation; therefore, replenishment of platelets from hematopoietic stem/progenitor cells (HSPCs) is needed to maintain the physiological level of circulating platelets. Platelet-derived microparticles (PMPs) are protein- and RNA-containing vesicles released from activated platelets. We hypothesized that factors carried by PMPs might influence the production of platelets from HSPCs, in a positive feedback fashion. Here we show that, during mouse acute liver injury, the density of megakaryocyte in the bone marrow increases following an increase in circulating PMPs, but without thrombopoietin (TPO) upregulation. In vitro, PMPs are internalized by HSPCs and drive them toward a megakaryocytic fate. Mechanistically, miR-1915-3p, a miRNA highly enriched in PMPs, is transported to target cells and suppresses the expression levels of Rho GTPase family member B, thereby inducing megakaryopoiesis. In addition, direct injection of PMPs into irradiated mice increases the number of megakaryocytes and platelets without affecting TPO levels. In conclusion, our data reveal that PMPs have a role in promoting megakaryocytic differentiation and platelet production. Platelets derive from megakaryocytes, which differentiate from hematopoietic stem/progenitor cells (HSPCs). Here, Qu et al show that platelet-derived microparticles carrying miR-1915-3p target HSPCs and promote megakaryopoiesis by suppressing RHOB expression levels. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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172. Low Initial Cell Density Promotes the Differentiation and Maturation of Human Pluripotent Stem Cells into Erythrocytes.
- Author
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Liang, Liqing, Xu, Lei, Dong, Qian, Zhang, Jing, Qu, Mingyi, Yuan, Xin, Zeng, Quan, Li, Huilin, Zhang, Bowen, Wang, Chao, Fan, Tao, He, Lijuan, Yue, Wen, Xie, Xiaoyan, and Pei, Xuetao
- Subjects
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PLURIPOTENT stem cells , *HUMAN stem cells , *ERYTHROCYTES , *METABOLIC regulation , *CELL culture , *BLOOD transfusion , *ERYTHROCYTE deformability - Abstract
Human pluripotent stem cell (hPSC)-derived red blood cells (RBCs) possess great potential for compensating shortages in transfusion medicine. For better RBC generation from hPSCs, we compared the cell seeding density in the embryoid body formation-based hPSC induction protocol. In the selection of low- and high-density inoculation conditions, we found that low-density culture performed better in the final RBC product with more cell output and increased average cellular hemoglobin content. An elaborate study using flow cytometry demonstrated that low inoculation density promoted endothelial-to-hematopoietic transition, followed by improved hematopoietic progenitor formation and erythrocyte generation. The improved transformation from glycolysis to mitochondrial oxidation and reduced apoptosis might be responsible for this effect. Hints from RNA sequencing suggested that molecules involved in microenvironment interaction and metabolic regulation might respond for the different developmental potential. The possible mediators between outer message and intracellular response could be the nutrition sensors FOXO, PRKAA1 (AMPK), and MTOR genes. It is possible that low inoculation density triggered metabolic regulation signals, promoted mitochondrial oxidation, and resulted in enhanced cell amplification and hematopoietic differentiation. The low cell culture density will improve RBC generation from hPSCs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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173. Establishment of human hematopoietic organoids for evaluation of hematopoietic injury and regeneration effect.
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Chen, Keyi, Li, Yunqiao, Wu, Xumin, Tang, Xuan, Zhang, Bowen, Fan, Tao, He, Lijuan, Pei, Xuetao, and Li, Yanhua
- Subjects
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HUMAN embryonic stem cells , *GRANULOCYTE-colony stimulating factor , *RADIATION damage , *BONE marrow , *ORGANOIDS , *BONE marrow diseases , *HEMATOPOIESIS - Abstract
Background: Human hematopoietic organoids have a wide application value for modeling human bone marrow diseases, such as acute hematopoietic radiation injury. However, the manufacturing of human hematopoietic organoids is an unaddressed challenge because of the complexity of hematopoietic tissues. Methods: To manufacture hematopoietic organoids, we obtained CD34+ hematopoietic stem and progenitor cells (HSPCs) from human embryonic stem cells (hESCs) using stepwise induction and immunomagnetic bead-sorting. We then mixed these CD34+ HSPCs with niche-related cells in Gelatin-methacryloyl (GelMA) to form a three-dimensional (3D) hematopoietic organoid. Additionally, we investigated the effects of radiation damage and response to granulocyte colony-stimulating factor (G-CSF) in hematopoietic organoids. Results: The GelMA hydrogel maintained the undifferentiated state of hESCs-derived HSPCs by reducing intracellular reactive oxygen species (ROS) levels. The established hematopoietic organoids in GelMA with niche-related cells were composed of HSPCs and multilineage blood cells and demonstrated the adherence of hematopoietic cells to niche cells. Notably, these hematopoietic organoids exhibited radiation-induced hematopoietic cell injury effect, including increased intracellular ROS levels, γ-H2AX positive cell percentages, and hematopoietic cell apoptosis percentages. Moreover, G-CSF supplementation in the culture medium significantly improved the survival of HSPCs and enhanced myeloid cell regeneration in these hematopoietic organoids after radiation. Conclusions: These findings substantiate the successful manufacture of a preliminary 3D hematopoietic organoid from hESCs-derived HSPCs, which was utilized for modeling hematopoietic radiation injury and assessing the radiation-mitigating effects of G-CSF in vitro. Our study provides opportunities to further aid in the standard and scalable production of hematopoietic organoids for disease modeling and drug testing. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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174. Integrative single-cell transcriptome analysis reveals a subpopulation of fibroblasts associated with favorable prognosis of liver cancer patients
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Wang, Haiyang, Feng, Chao, Lu, Meixin, Zhang, Biao, Xu, Yingchen, Zeng, Quan, Xi, Jiafei, Zhou, Junnian, Ying, Xiaomin, Zhang, Jian, Yue, Wen, and Pei, Xuetao
- Abstract
•Integrative single-cell transcriptome analysis reveals the accumulation of fibroblasts in liver cancer tissues.•SPARCL1expression distinguishes two subpopulations of the liver cancer-distinct fibroblasts.•SPARCL1positive fibroblasts are related to favorable prognosis of liver cancer patients.
- Published
- 2021
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175. Baffled‐flow culture system enables the mass production of megakaryocytes from human embryonic stem cells by enhancing mitochondrial function.
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Wu, Xumin, Zhang, Bowen, Chen, Keyi, Zhao, Jiahui, Li, Yunxing, Li, Jisheng, Liu, Chuanli, He, Lijuan, Fan, Tao, Wang, Chao, Li, Yan, Pei, Xuetao, and Li, Yanhua
- Subjects
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HUMAN embryonic stem cells , *MASS production , *EMBRYONIC stem cells , *MEGAKARYOCYTES , *THROMBOPOIETIN receptors , *AUTOMATION , *MITOCHONDRIA , *CELL culture - Abstract
Human embryonic stem cells (hESCs) have become an ideal cell source for the ex vivo generation of megakaryocyte (MK) and platelet products for clinical applications. However, an ongoing challenge is to establish scalable culture systems to maximize the yield of stem cell‐derived MKs that release platelets. We defined a specific dynamic 3D manufacturing system in a baffled‐flow manner that could remarkably facilitate megakaryopoiesis and increase the yield of platelet‐producing MKs from hESCs within a 12‐day induction period. Additionally, an increased number of >16N ploidy MKs, proplatelets, and platelets were generated from induced cells harvested on Day 12 using the specific dynamic culture method. The specific dynamic culture method significantly enhanced endothelium‐to‐haematopoietic transition and early haematopoiesis. More importantly, MK fate was significantly facilitated in a specific dynamic manner during early haematopoiesis. Mechanistically, this dynamic culture significantly enhanced mitochondrial function via the oxidative phosphorylation pathway and caused differentiation skewing of hESCs toward megakaryopoiesis. This study can aid in the automatic and scalable production of MKs from stem cells using baffled‐flow bioreactors and assist in the manufacturing of hESC‐derived MK and platelet products. [ABSTRACT FROM AUTHOR]
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- 2023
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176. Generation of Rh D‐negative blood using CRISPR/Cas9.
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Xu, Lei, Zeng, Quan, Liang, Liqing, Yang, Zhou, Qu, Mingyi, Li, Huilin, Zhang, Bowen, Zhang, Jing, Yuan, Xin, Chen, Lin, Fan, Zeng, He, Lijuan, Nan, Xue, Yue, Wen, Xie, Xiaoyan, and Pei, Xuetao
- Subjects
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ERYTHROCYTES , *CRISPRS , *INDUCED pluripotent stem cells , *BLOOD groups , *PROGENITOR cells , *MANUFACTURING cells - Abstract
Blood supply shortages, especially the shortage of rare blood types, threaten the current medical system. Research on stem cells has shed light on in vitro blood cell manufacturing. The in vitro production of universal red blood cells (RBCs) from induced pluripotent stem cells (iPSCs) has become the focus of transfusion medicine. To obtain O‐type Rh D‐negative blood, we developed O‐type Rh D‐negative human (h)iPSCs using homology‐directed repair (HDR)‐based CRISPR/Cas9. HuAiPSCs derived from human umbilical arterial endothelial cells and showing haematopoietic differentiation preferences were selected for gene modification. Guide RNAs (gRNAs) were selected, and a donor template flanked by gRNA‐directed homologous arms was set to introduce a premature stop code to RHD exon 2. CRISPR/Cas9 gene editing has resulted in the successful generation of an RHD knockout cell line. The HuAiPSC‐A1‐RHD−/− cell line was differentiated into haematopoietic stem/progenitor cells and subsequently into erythrocytes in the oxygen concentration‐optimized differentiation scheme. HuAiPSC‐A1‐RHD−/− derived erythrocytes remained positive for the RBC markers CD71 and CD235a. These erythrocytes did not express D antigen and did not agglutinate in the presence of anti‐Rh D reagents. In conclusion, taking the priority of haematopoietic preference hiPSCs, the HDR‐based CRISPR/Cas9 system and optimizing the erythroid‐lineage differentiation protocol, we first generated O‐type Rh D‐negative universal erythrocytes from RHD knockout HuAiPSCs. Its production is highly efficient and shows great potential for clinical applications. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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177. Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells.
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Qin, Jinhua, Chang, Mingyang, Wang, Shuyong, Liu, Zhenbo, Zhu, Wei, Wang, Yi, Yan, Fang, Li, Jian, Zhang, Bowen, Dou, Guifang, Liu, Jiang, Pei, Xuetao, and Wang, Yunfang
- Abstract
Gap junction-mediated cell-cell interactions are highly conserved and play essential roles in cell survival, proliferation, differentiation and patterning. We report that Connexin 32 (Cx32)-mediated gap junctional intercellular communication (GJIC) is necessary for human embryonic stem cell-derived hepatocytes (hESC-Heps) during step-wise hepatic lineage restriction and maturation. Vitamin K2, previously shown to promote Cx32 expression in mature hepatocytes, up-regulated Cx32 expression and GJIC activation during hepatic differentiation and maturation, resulting in significant increases of hepatic markers expression and hepatocyte functions. In contrast, negative Cx32 regulator 2-aminoethoxydiphenyl borate blocked hESC-to-hepatocyte maturation and muted hepatocyte functions through disruption of GJIC activities. Dynamic gap junction organization and internalization are phosphorylation-dependent and the p38 mitogen-activated protein kinases pathway (MAPK) can negatively regulate Cxs through phosphorylation-dependent degradation of Cxs. We found that p38 MAPK inhibitor SB203580 improved maturation of hESC-Heps correlating with up-regulation of Cx32; by contrast, the p38 MAPK activator, anisomycin, blocked hESC-Heps maturation correlating with down-regulation of Cx32. These results suggested that Cx32 is essential for cell-cell interactions that facilitate driving hESCs through hepatic-lineage maturation. Regulators of both Cx32 and other members of its pathways maybe used as a promising approach on regulating hepatic lineage restriction of pluripotent stem cells and optimizing their functional maturation. [ABSTRACT FROM AUTHOR]
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- 2016
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178. miR-125b modulates megakaryocyte maturation by targeting the cell-cycle inhibitor p19INK4D.
- Author
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Qu, Mingyi, Fang, Fang, Zou, Xiaojing, Zeng, Quan, Fan, Zeng, Chen, Lin, Yue, Wen, Xie, Xiaoyan, and Pei, Xuetao
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- 2016
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179. Superior osteogenic capacity of different mesenchymal stem cells for bone tissue engineering.
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Wen, Yong, Jiang, Baoqi, Cui, Jun, Li, Guoju, Yu, Meijiao, Wang, Fang, Zhang, Gairong, Nan, Xue, Yue, Wen, Xu, Xin, and Pei, Xuetao
- Abstract
Objective: We evaluated the effect of human bone marrow stromal cells (hBMSCs), human adipose tissue–derived mesenchymal stem cells (hAD-MSCs), and umbilical cord–derived mesenchymal stem cells (hUC-MSCs) in bone tissue engineering and identified a reliable cell source. Study Design: Alkaline phosphatase (ALP) activity and quantitative polymerase chain reaction were used to evaluate osteogenic in vitro, X-ray and histologic analysis in vivo. Results: hBMSCs exhibited strongest ALP staining, followed by hAD-MSCs and hUC-MSCs. At 7 days, hUC-MSCs and hAD-MSCs had higher expression of collagen type I and Runt-related transcription factor 2 than hBMSCs, and hUC-MSCs showed higher osteopontin expression. Bone structure was observed in the hUC-MSC group. Defects showed good healing in the hBMSC and hAD-MSC groups. Enhanced green fluorescent protein and osteopontin were detected in newly formed bone at 8 weeks. Conclusions: Our results suggested that hUC-MSCs and hAD-MSCs could be used for bone tissue engineering effectively; hUC-MSCs could serve as a new alternative cell source. [Copyright &y& Elsevier]
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- 2013
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180. In vitro large scale production of human mature red blood cells from hematopoietic stem cells by coculturing with human fetal liver stromal cells.
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Xi, Jiafei, Li, Yanhua, Wang, Ruoyong, Wang, Yunfang, Nan, Xue, He, Lijuan, Zhang, Peng, Chen, Lin, Yue, Wen, and Pei, Xuetao
- Abstract
In vitro models of human erythropoiesis are useful in studying the mechanisms of erythroid differentiation in normal and pathological conditions. Here we describe an erythroid liquid culture system starting from cord blood derived hematopoietic stem cells (HSCs). HSCs were cultured for more than 50 days in erythroid differentiation conditions and resulted in a more than 10(9)-fold expansion within 50 days under optimal conditions. Homogeneous erythroid cells were characterized by cell morphology, flow cytometry, and hematopoietic colony assays. Furthermore, terminal erythroid maturation was improved by cosculturing with human fetal liver stromal cells. Cocultured erythroid cells underwent multiple maturation events, including decrease in size, increase in glycophorin A expression, and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to 80% of the cells. Importantly, they possessed the capacity to express the adult definitive ß -globin chain upon further maturation. We also show that the oxygen equilibrium curves of the cord blood-differentiated red blood cells (RBCs) are comparable to normal RBCs. The large number and purity of erythroid cells and RBCs produced from cord blood make this method useful for fundamental research in erythroid development, and they also provide a basis for future production of available RBCs for transfusion. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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181. An optimized method for obtaining clinical‐grade specific cell subpopulations from human umbilical cord‐derived mesenchymal stem cells.
- Author
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Jia, Yali, Wang, Ailin, Zhao, Bichun, Wang, Chao, Su, Ruyu, Zhang, Biao, Fan, Zeng, Zeng, Quan, He, Lijuan, Pei, Xuetao, and Yue, Wen
- Subjects
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MESENCHYMAL stem cells , *CELL culture , *UMBILICAL cord , *CELL survival , *TREATMENT effectiveness , *CELLULAR therapy - Abstract
Mesenchymal stem cells (MSCs) are heterogeneous populations with broad application prospects in cell therapy, and using specific subpopulations of MSCs can enhance their particular capability under certain conditions and achieve better therapeutic effects. However, no studies have reported how to obtain high‐quality specific MSC subpopulations in vitro culture. Here, for the first time, we established a general operation process for obtaining high‐quality clinical‐grade cell subpopulations from human umbilical cord MSCs (hUC‐MSCs) based on particular markers. We used the MSC‐CD106+ subpopulations, whose biological function has been well documented, as an example to explore and optimize the crucial links of primary preparation, pre‐treatment, antibody incubation, flow sorting, quality and function test. After comprehensively evaluating the quality and function of the acquired MSC‐CD106+ subpopulations, including in vitro cell viability, apoptosis, proliferation, marker stability, adhesion ability, migration ability, tubule formation ability, immunomodulatory function and in vivo wound healing ability and proangiogenic activity, we defined an important pre‐treatment scheme which might effectively improve the therapeutic efficiency of MSC‐CD106+ subpopulations in two critical clinical application scenarios—direct injection after cell sorting and post‐culture injection into bodies. Based on the above, we tried to establish a general five‐step operation procedure for acquiring high‐quality clinical‐grade MSC subpopulations based on specific markers, which cannot only improve their enrichment efficiency and the reliability of preclinical studies, but also provide valuable methodological guidance for the rapid clinical transformation of specific MSC subpopulations. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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182. Requirements for human cardiomyocytes.
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Yu, Miao, Lei, Wei, Cao, Jiani, Wang, Lei, Ma, Aijin, Zhao, Zhen‐Ao, Yang, Huang‐Tian, Shen, Zhenya, Lan, Feng, Cao, Feng, Liang, Ping, Pei, Xuetao, Xiang, Andy Peng, Yu, Junying, Zhang, Yu, Zhang, Yong, Li, Qiyuan, Zhou, Jiaxi, Wei, Jun, and Peng, Yaojin
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STANDARDIZATION , *STEM cell research , *HUMAN beings - Abstract
'Requirements for human cardiomyocytes', jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human cardiomyocytes in China. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packing requirements, storage requirements, transportation requirements and waste disposal requirements for human cardiomyocytes, which is designed to normalize and standardize human cardiomyocyte research and production. It was originally released by the China Society for Cell Biology on 9 January 2021. We hope that the publication of this guideline will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human cardiomyocytes for applications. [ABSTRACT FROM AUTHOR]
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- 2022
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183. Ricolinostat promotes the generation of megakaryocyte progenitors from human hematopoietic stem and progenitor cells.
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Jiang, Jianan, Qin, Jinhua, Li, Jisheng, Lin, Xiaosong, Zhang, Bowen, Fan, Zeng, He, Lijuan, Zeng, Quan, Yue, Wen, Zheng, Min, Pei, Xuetao, and Li, Yanhua
- Subjects
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PROGENITOR cells , *STEM cells , *CELL determination , *SMALL molecules , *HIGH throughput screening (Drug development) , *CORD blood - Abstract
Background: Ex vivo production of induced megakaryocytes (MKs) and platelets from stem cells is an alternative approach for supplying transfusible platelets. However, it is difficult to generate large numbers of MKs and platelets from hematopoietic stem cells and progenitor cells (HSPCs). Methods: To optimize the differentiation efficiency of megakaryocytic cells from HSPCs, we first employed a platelet factor 4 (PF4)-promoter reporter and high-throughput screening strategy to screen for small molecules. We also investigated the effects and possible mechanisms of candidate small molecules on megakaryocytic differentiation of human HSPCs. Results: The small molecule Ricolinostat remarkably promoted the expression of PF4-promoter reporter in the megakaryocytic cell line. Notably, Ricolinostat significantly enhanced the cell fate commitment of MK progenitors (MkPs) from cord blood HSPCs and promoted the proliferation of MkPs based on cell surface marker detection, colony-forming unit-MK assay, and quantitative real-time PCR analyses. MkPs generated from Ricolinostat-induced HSPCs differentiated into mature MKs and platelets. Mechanistically, we found that Ricolinostat enhanced MkP fate mainly by inhibiting the secretion of IL-8 and decreasing the expression of the IL-8 receptor CXCR2. Conclusion: The addition of Ricolinostat to the culture medium promoted MkP differentiation from HSPCs and enhanced the proliferation of MkPs mainly by suppressing the IL-8/CXCR2 pathway. Our results can help the development of manufacturing protocols for the efficient generation of MKs and platelets from stem cells in vitro. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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184. Differentiation of human embryonic stem cells along a hepatocyte lineage and its application in liver regeneration.
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Pei Haiyun, Wang Yun Fang, and Pei Xuetao
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EMBRYONIC stem cells , *LIVER regeneration , *LIVER transplantation , *LIVER cells , *LIVER diseases - Abstract
Hepatocyte transplantation and bioartificial liver (BAL) as alternatives to liver transplantation offer the possibility of effective treatment for many inherited and acquired hepatic disorders. Unfortunately, the limited availability of donated livers and the variability of their derived hepatocytes make it difficult to obtain enough viable human hepatocytes for the hepatocyte-based therapies. Embryonic stem cells (ESCs), which could be isolated directly from the blastocyst inner cell mass, have permanent self-renewal capability and developmental pluripotency and therefore might be an ideal cell source in the treatment of hepatic discords. However, differentiation of hESCs into hepatocytes with significant numbers remains a challenge. This review updates our current understanding of differentiation of ESCs into hepatic lineage cells, their future therapeutic uses and problems in liver regeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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185. Large‐scale generation of megakaryocytes from human embryonic stem cells using transgene‐free and stepwise defined suspension culture conditions.
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Zhang, Bowen, Wu, Xumin, Zi, Guicheng, He, Lijuan, Wang, Sihan, Chen, Lin, Fan, Zeng, Nan, Xue, Xi, Jiafei, Yue, Wen, Wang, Lei, Wang, Liu, Hao, Jie, Pei, Xuetao, and Li, Yanhua
- Subjects
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HUMAN embryonic stem cells , *EMBRYONIC stem cells , *CANCER cell culture , *MEGAKARYOCYTES , *HUMAN stem cells , *PLURIPOTENT stem cells - Abstract
Objectives: Ex vivo engineered production of megakaryocytes (MKs) and platelets (PLTs) from human pluripotent stem cells is an alternative approach to solve shortage of donor‐donated PLTs in clinics and to provide induced PLTs for transfusion. However, low production yields are observed and the generation of clinically applicable MKs and PLTs from human pluripotent stem cells without genetic modifications still needs to be improved. Materials and Methods: We defined an optimal, stepwise and completely xeno‐free culture protocol for the generation of MKs from human embryonic stem cells (hESCs). To generate MKs from hESCs on a large scale, we improved the monolayer induction manner to define three‐dimensional (3D) and sphere‐like differentiation systems for MKs by using a special polystyrene CellSTACK culture chamber. Results: The 3D manufacturing system could efficiently generate large numbers of MKs from hESCs within 16‐18 days of continuous culturing. Each CellSTACK culture chamber could collect on an average 3.4 × 108 CD41+ MKs after a three‐stage orderly induction process. MKs obtained from hESCs via 3D induction showed significant secretion of IL‐8, thrombospondin‐1 and MMP9. The induced cells derived from hESCs in our culture system were shown to have the characteristics of MKs as well as the function to form proPLTs and release PLTs. Furthermore, we generated clinically applicable MKs from clinical‐grade hESC lines and confirmed the biosafety of these cells. Conclusions: We developed a simple, stepwise, 3D and completely xeno‐free/feeder‐free/transgene‐free induction system for the generation of MKs from hESCs. hESC‐derived MKs were shown to have typical MK characteristics and PLT formation ability. This study further enhances the clinical applications of MKs or PLTs derived from pluripotent stem cells. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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186. Combining chitin biological conduits with injectable adipose tissue-derived decellularised matrix hydrogels loaded with adipose-derived mesenchymal stem cells for the repair of peripheral nerve defects in rats.
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Li, Yan, Chen, Zhaoyang, Zhou, Junnian, Guan, Yanjun, Xing, Jiahua, Niu, Zehao, Zhang, Biao, Zeng, Quan, Pei, Xuetao, Wang, Yu, Peng, Jiang, Xu, Wenjing, Yue, Wen, and Han, Yan
- Subjects
- *
MESENCHYMAL stem cells , *NERVOUS system regeneration , *PERIPHERAL nerve injuries , *SCIATIC nerve injuries , *NERVOUS system injuries , *SCIATIC nerve , *ADIPOSE tissues - Abstract
Mesenchymal stem cells (MSCs) have shown potential for the repair of defective tissues and peripheral nerve injuries. However, local treatment alone may lead to cell loss, low viability, and diminished paracrine action owing to the lack of effective biological scaffolds. To improve the therapeutic effects of MSCs, bioactive scaffolds that mimic the stem cell microenvironment in vivo should be constructed. We developed an injectable decellularised matrix hydrogel (DAM-gel) to simulate the stem cell microenvironment using combined physical, chemical, and enzymatic digestions of human adipose tissues. The DAM-gel was loaded with rat adipose-derived mesenchymal stem cells (ADSCs) to repair sciatic nerve defects. Compared with ADSCs alone, the ADSC-loaded DAM-gel promoted the proliferation of Schwann cells in vitro, which are important in sciatic nerve regeneration. Chitin biological conduits filled with ADSC-DAM-gel composites were designed to bridge the sciatic nerve defects. Axonal regeneration and the recovery of neurological function in the ADSC-DAM-gel group increased post-surgery compared with the control group (blank conduit, ADSCs, and DAM-gel group), as confirmed by a CatWalk gait analysis, electrophysiology, and nerve/muscle histology. The ADSC-loaded DAM-gel-treated rats retained the improved peripheral nerve regeneration. Therefore, DAM-gels have great potential for enhancing the repair capacity of ADSCs in peripheral nerve defects. [Display omitted] • Fabricated DAM-gel is a thermosensitive material with a loose network structure. • It has strong biocompatibility and rheological properties, ideal for NGC filling. • In vitro co-culture of DAM-gel-loaded ADSCs increased SC proliferative activity. • In vivo transplantation of DAM-gel-loaded ADSCs promotes axonal regeneration. • It promotes recovery of motor function after 10 mm sciatic nerve injury in rats. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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187. Biomimetic Prussian blue nanozymes with enhanced bone marrow-targeting for treatment of radiation-induced hematopoietic injury.
- Author
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Zhang, Bowen, Chen, Gan, Wu, Xumin, Li, Yunxing, Xiao, Yao, Li, Jisheng, He, Lijuan, Li, Yunqiao, Wang, Sihan, Zhao, Jiahui, Liu, Chuanli, Zhou, Hong, Li, Yanhua, and Pei, Xuetao
- Subjects
- *
PRUSSIAN blue , *SYNTHETIC enzymes , *BONE marrow cells , *HEMATOPOIETIC stem cells , *MESENCHYMAL stem cells , *IRRADIATION , *BIOMIMETIC materials - Abstract
There is an urgent medical need to develop effective therapies that can ameliorate damage to the radiation-exposed hematopoietic system. Nanozymes with robust antioxidant properties have a therapeutic potential for mitigating radiation-induced hematopoietic injury. However, enhancing nanozyme recruitment to injured tissues in vivo while maintaining their catalytic activity remains a great challenge. Herein, we present the design and preparation of a biomimetic nanoparticle, a mesenchymal stem cell membrane camouflaged Prussian blue nanozyme (PB@MSCM), which exhibits biocompatible surface properties and demonstrates enhanced injury site-targeting towards the irradiated murine bone marrow niche. Notably, the constructed PB@MSCM possessed redox enzyme-mimic catalytic activity and could scavenge overproduced reactive oxygen species in the irradiated bone marrow cells, both in vitro and ex vivo. More importantly, the administration of PB@MSCM significantly mitigated hematopoietic cell apoptosis and accelerated the regeneration of hematopoietic stem and progenitor cells. Our findings provide a new targeted strategy to improve nanozyme therapy in vivo and mitigate radiation-induced hematopoietic injury. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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188. Involvement of RhoA/ROCK in insulin secretion of pancreatic β-cells in 3D culture.
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Liu, Xiaofang, Yan, Fang, Yao, Hailei, Chang, Mingyang, Qin, Jinhua, Li, Yali, Wang, Yunfang, and Pei, Xuetao
- Subjects
- *
PANCREATIC beta cells , *CELL culture , *EXOCYTOSIS , *GENETIC regulation , *LABORATORY mice - Abstract
Cell-cell contacts and interactions between pancreatic β-cells and/or other cell populations within islets are essential for cell survival, insulin secretion, and functional synchronization. Three-dimensional (3D) culture systems supply the ideal microenvironment for islet-like cluster formation and functional maintenance. However, the underlying mechanisms remain unclear. In this study, mouse insulinoma 6 (MIN6) cells were cultured in a rotating 3D culture system to form islet-like aggregates. Glucose-stimulated insulin secretion (GSIS) and the RhoA/ROCK pathway were investigated. In the 3D-cultured MIN6 cells, more endocrine-specific genes were up-regulated, and GSIS was increased to a greater extent than in cells grown in monolayers. RhoA/ROCK inactivation led to F-actin remodeling in the MIN6 cell aggregates and greater insulin exocytosis. The gap junction protein, connexin 36 (Cx36), was up-regulated in MIN6 cell aggregates and RhoA/ROCK-inactivated monolayer cells. GSIS dramatically decreased when Cx36 was knocked down by short interfering RNA and could not be reversed by RhoA/ROCK inactivation. Thus, the RhoA/ROCK signaling pathway is involved in insulin release through the up-regulation of Cx36 expression in 3D-cultured MIN6 cells. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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189. Three-dimensional cultivation of human adipose-derived stem cells with human decellularized adipose tissue matrix scaffold promotes diabetic wound healing.
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Ren, Jing, Chi, Jinghan, Wang, Baishi, Guo, Lingli, Han, Yudi, Liu, Xinhui, Pei, Xuetao, Yue, Wen, and Han, Yan
- Subjects
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HUMAN stem cells , *WOUND healing , *TISSUE scaffolds , *VASCULAR endothelial cells , *ADIPOSE tissues , *ENDOTHELIAL cells , *BLOOD volume , *CELL suspensions - Abstract
Diabetic wounds are a worldwide health problem, with increasing morbidity and risk of amputation. This study investigated a novel application of a human decellularized adipose tissue matrix (hDAM) as a natural 3D scaffold for delivering human adipose-derived stem cells (hASCs) to diabetic wounds. The porous structure, ability to preserve extracellular matrix components, and convenient storage conditions of decellularized hDAM make it a potential clinical wound dressing material. The hASCs cultured in the hDAM scaffold exhibited a fibroblast-like morphology and more evenly distributed cells on both the surface and inside the porous structure of the hDAM scaffold. In addition, the biocompatibility of hDAM enhanced the hASCs proliferation, maintenance of the stemness properties, and release of angiogenic cytokines compared to those under standard culture conditions. Moreover, cell suspensions derived from hASCs cultured in hDAM scaffolds promoted the proliferation and migration of human umbilical vascular endothelial cells, indicating its potential effect in promoting angiogenesis. Furthermore, the potential clinical therapeutic efficacy of the hASC-hDAM composite for diabetic wound healing was evaluated using a full-thickness wound model in diabetic mice. Diabetic rats treated with the hASCs-seeded hDAM scaffold displayed enhanced wound healing efficiency, including an improved blood perfusion volume for wounds, reduced number of inflammatory cells, and enhanced epithelization. This study demonstrated that the 3D model that combined hASCs and an hDAM could accelerate wound healing and might hold potential for clinical application to enhance diabetic wound healing and regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2022
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- View/download PDF
190. Author Correction: Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells.
- Author
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Qin, Jinhua, Chang, Mingyang, Wang, Shuyong, Liu, Zhenbo, Zhu, Wei, Wang, Yi, Yan, Fang, Li, Jian, Zhang, Bowen, Dou, Guifang, Liu, Jiang, Pei, Xuetao, and Wang, Yunfang
- Subjects
- *
EMBRYONIC stem cells , *CELL communication - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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191. In vitro differentiation of human adipose-derived mesenchymal stem cells into endothelial-like cells.
- Author
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Guan Lidong, Li Shaoqing, Wang Yunfang, Yue Huimin, Liu Daqing, He Lijuan, Bai Cixian, Yan Fang, Nan Xue, Shi Shuangshuang, and Pei Xuetao
- Subjects
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STEM cells , *ADIPOSE tissues , *CELLULAR therapy , *NEOVASCULARIZATION , *ISCHEMIA - Abstract
The neovascularization of ischemic tissue is a crucial initial step for the functional rehabilitation and wound healing. However, the short of seed cell candidate for the foundation of vascular network is still a big issue. Human adipose tissue derived mesenchymal stem cells (hADSCs), which possess multilineage potential, are capable of adipogenic, osteogenic, and chondrogenic differentiation. We examined whether this kind of stem cells could differentiate into endothelial-like cells and participate in blood vessel formation, and whether they could be used as an ideal cell source for therapeutic angiogenesis in ischemic diseases or vascularization of tissue constructs. The results showed that hADSCs, grown under appropriately induced conditions, displayed characteristics similar to those of vessel endothelium. The differentiated cells expressed endothelial cell markers CD34 and vWF, and had high metabolism of acetylated low-density lipoprotein and prostacyclin. In addition, the induced cells were able to form tube-like structures when cultured on matrigel. Our data indicated that induced hADSCs could exhibit characteristics of endothelial cells. Therefore, these cells, as a source of human endothelial cells, may find many applications in such realms as engineering blood vessels, endothelial cell transplantation for myocardial regeneration, and induction of angiogenesis for treatment of regional ischemia. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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192. Isolation and analysis of SSEA-4 positive cells derived from fetal marrow mesenchymal stem cells.
- Author
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LIU Daqing, YANG Yinxiang, GAO Yanhong, YUAN Hongfeng, QIN Lipeng, WANG Yunfang, NAN Xue, SHI Shuangshuang, YUE Wen, and PEI Xuetao
- Subjects
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MESENCHYMAL stem cells , *STEM cell research , *CARCINOGENICITY , *GENE expression , *REGENERATIVE medicine , *VACCINATION , *LABORATORY mice - Abstract
A big issue in stem cell research is to derive prospective totipotential stem cells. In this study, fMSC-SSEA-4 cells expressing SSEA-4 antigen were isolated from fetal marrow masenchymal stem cells (fMSCs) using immunomagnetic bead sorting technique. The totipotent cells were identified and their biological characteristics were further studied. The expression of Oct-4 and SSEA-4, carcinogenicity, and the ability to differentiation of fMSC-SSEA-4 cells were evaluated to verify the totipotent potential. fMSC-SSEA-4 cells were isolated successfully from fMSCs (2.5% among fMSCs), while no obvious differences were seen in morphology, growth curve, cell cycle and immunophenotype, Oct-4 and SSEA-4 expression between fMSC-SSEA-4 cells and fMSCs. fMSC-SSEA-4 cells showed normal diploid chromosome karyotype and no carcinoma was induced after inoculation into nude mice. fMSC-SSEA-4 cells could be induced to fat cells, osteogenic cells and neuron-like cells in vitro with different induced factors. The results indicated that there may be a few totipotent cells among the fMSCs and it may offer the experimental basis for the further study and application of fMSCs. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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193. Proliferation and differentiation into endothelial cells of human bone marrow mesenchymal stem cells (MSCs) on poly DL-lactic-co-glycolic acid (PLGA) films.
- Author
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Yue Huimin, Zhang Lei, Wang Yunfang, Liang Feng, Guan Lidong, Li Shaoqing, Yan Fang, Nan Xue, Bai Cixian, Lin Feng, Van Yongnian, and Pei Xuetao
- Subjects
- *
VASCULAR endothelium , *STEM cells , *CELL proliferation , *CELL growth , *LOW density lipoproteins , *PROSTACYCLIN - Abstract
The functional realization is the most important problem in vascular tissue engineering. The small-caliber blood vessel substitutes are prone to thrombi, which results in functional loss of blood vessels. However, this is probably due to the imperfection of endothelial layer in the substitutes. In this study, MSCs were seeded on a series of porous PLGA films with various porosity and pore size made by sodium chloride (NaCl) particulate leaching, and cell proliferation on each film was inspected. The film made of the 75% (w/w) particulate proportion and 30–50 μm pore size maximized the proliferation rate and was chosen as the scaffolds for the differentiation of MSCs into endothelial cells. The induced cells expressed endothelial cells specific Flk-1, VIII factor and CD34, possessed endothelial cells specific Weible-palade (W-P) body, and had the abilities of ingesting low density lipoprotein and secreting prostacyclin (PGI2). The results show that MSCs not only have the ideal biological compatibility with the porous PLGA films, but also have the potency of differentiating into functional endothelial cells, which should facilitate the endothelialization in vascular tissue engineering. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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194. A novel human gene spindlin 1, encoding a protein localized in the cell nucleus and inducing NIH3T3 cell' s transformation.
- Author
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Gao Yanhong, Qin Lipeng, Zhang Peng, Chen Lin, Yuan Hongfeng, Bai Cixian, Yan Fang, Yue Wen, and Pei Xuetao
- Subjects
- *
GENES , *MOLECULAR genetics , *MORPHOLOGY , *CARCINOGENESIS , *PROTEINS , *CELL transformation - Abstract
A novel human gene, spindlin 1, recently cloned in our laboratory, is highly expressed in the tissue of ovary cancer. To study its biological function, a vector expressing green fluorescent-spindlin 1 fusion protein was constructed and transfected into COS-7 and NIH3T3 cells by lipofectamine methods. The results showed that the fusion protein pEGFP-N1-spindlin 1 was localized in the nucleus of COS-7 and NIH3T3 cells. NIH3T3 cells which could stably express spindlin 1 as a result of RT-PCR analysis compared with the parental NIH3T3 cells displayed a complete morphological change, improved the cell growth and increased the percentage of cells in G2/M phase (12.6% vs control cells at 3.4%). Furthermore, overexpressed spindlin 1 cells formed colonies in soft agar, more motile in migration assay in vitro and formed tumors in nude mice. Our findings provide direct evidence that spindlin 1 gene may be a prooncogene which is associated with tumorigenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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195. Inducing dopaminergic differentiation of expanded rat mesencephalic neural stem cells by ascorbic acid in vitro.
- Author
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Zheng Min, Wang Dongmei, Hou Lingling, Li Haimin, Xie Chao, Jiao Wencang, Bai Cixian, Wang Yaping, and Pei Xuetao
- Subjects
- *
PARKINSON'S disease , *DOPAMINERGIC mechanisms , *SYMPATHETIC nervous system , *NEURAL stem cells , *VITAMIN C , *FIBROBLAST growth factors , *EPIDERMAL growth factor , *NEUROTRANSMITTERS - Abstract
Abstract Ascorbic acid (AA) induced differentiation of neural stem cells (NSCs) into dopaminergic (DAergic) neurons is reported. NSCs derived from rat mesencephalon were maintained and expanded in a defined medium containing mitogens of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Compared with the control, ascorbic acid treatment led to more DAergic neuronal differentiation as indicated by the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT), which are specific markers of dopamine neurons. AA induction also enhanced expression of Nurr1 and Shh. PD98059, an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, could block AA-induced Nurr1, TH and DAT mRNA expression. The results might suggest a new strategy to provide enough dopaminergic cells for the therapy of Parkinson' s disease (PD), and Nurr1 and ERK signaling pathway might participate in the AA-induced DAergic differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
196. Injectable human decellularized adipose tissue hydrogel containing stem cells enhances wound healing in mouse.
- Author
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Pu, Wenwen, Ren, Jing, Chen, Youbai, Shu, Jun, Cui, Lei, Han, Yudi, Xi, Jiafei, Pei, Xuetao, Yue, Wen, and Han, Yan
- Subjects
- *
STEM cells , *HUMAN stem cells , *ADIPOSE tissues , *HYDROGELS , *WOUND healing , *NEPRILYSIN , *ECOLOGICAL niche , *MICE - Abstract
• We successfully produced a thermal sensitive hDAT-gel. • The hDAT-gel supports hASCs culture in vitro. • The hDAT-gel containing hASCs has wound healing efficacy. Acellular matrix hydrogels have been extracted from a variety of tissues currently, which have been widely exploited for various applications. What is more, hydrogels derived from porcine myocardium matrix have entered clinical trials (NCT02305602) for the prevention and treatment of heart failure post-myocardial infarction. However, few scholars have analyzed the adipose acellular matrix hydrogels. Here we report an injectable hydrogel entirely from human decellularized adipose tissue (hDAT-gel) and explore the innovative application in wound healing combining with human adipose-derived stem cells (hASCs). We postulated that hDAT-gel could provide hASCs with a 3D vivo-like ecological niche necessary to enhance stem cell engraftment, survival as well as differentiation to improve the quality of wound healing. Consequently, a temperature-responsive hDAT-gel was successfully produced, which could undergo sol-gel transition at 37℃. In vitro, hASCs could survive and proliferate well in the self-assembled gel which retained important protein components. In vivo, when the hASCs-embedded hDAT-gels were injected into the full-thickness cutaneous wound of mice, the wound healed rapidly through obvious neovascularization especially within 7 days. Our study demonstrated that the hDAT-gel containing hASCs could accelerate the vascularization of the wound site and speed up the wound healing to some extent. It is a promising injectable biomaterial for stem cell delivery and wound repair. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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197. Clinical-grade human umbilical cord-derived mesenchymal stem cells improved skeletal muscle dysfunction in age-associated sarcopenia mice.
- Author
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Wang C, Zhao B, Zhai J, Wang A, Cao N, Liao T, Su R, He L, Li Y, Pei X, Jia Y, and Yue W
- Subjects
- Humans, Mice, Animals, Aged, Cell Differentiation, Muscle, Skeletal, Extracellular Matrix Proteins metabolism, Umbilical Cord, Sarcopenia therapy, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cell Transplantation methods
- Abstract
With the expansion of the aging population, age-associated sarcopenia (AAS) has become a severe clinical disease of the elderly and a key challenge for healthy aging. Regrettably, no approved therapies currently exist for treating AAS. In this study, clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were administrated to two classic mouse models (SAMP8 mice and D-galactose-induced aging mice), and their effects on skeletal muscle mass and function were investigated by behavioral tests, immunostaining, and western blotting. Core data results showed that hUC-MSCs significantly restored skeletal muscle strength and performance in both mouse models via mechanisms including raising the expression of crucial extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging. For the first time, the study comprehensively evaluates and demonstrates the preclinical efficacy of clinical-grade hUC-MSCs for AAS in two mouse models, which not only provides a novel model for AAS, but also highlights a promising strategy to improve and treat AAS and other age-associated muscle diseases. This study comprehensively evaluates the preclinical efficacy of clinical-grade hUC-MSCs in treating age-associated sarcopenia (AAS), and demonstrates that hUC-MSCs restore skeletal muscle strength and performance in two AAS mouse models via raising the expression of extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging, which highlights a promising strategy for AAS and other age-associated muscle diseases., (© 2023. The Author(s).)
- Published
- 2023
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- View/download PDF
198. Preferential Hematopoietic Differentiation in Induced Pluripotent Stem Cells Derived From Human Umbilical Cord Arterial Endothelial Cells.
- Author
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Pei H, Li H, Xu L, Zhang B, Zhang H, Jia Y, Liang L, Xie X, Fan Z, Yang Z, Wang X, Song F, He L, Yue W, and Pei X
- Subjects
- Humans, Endothelial Cells metabolism, Cell Differentiation genetics, Umbilical Cord, Cellular Reprogramming, Induced Pluripotent Stem Cells metabolism, Pluripotent Stem Cells
- Abstract
Background: The major obstacle for applications of human induced pluripotent stem cells (hiPSCs) is efficient and controlled lineage-specific differentiation. Hence, a deeper understanding of the initial populations of hiPSCs is required to instruct proficient lineage commitment., Methods: hiPSCs were generated from somatic cells by transduction of 4 human transcription factors (OCT4, SOX2, KLF4, and C-MYC) using Sendai virus vectors. Genome-wide DNA methylation analysis and transcriptional analysis were performed to evaluate the pluripotent capacity and somatic memory state of hiPSCs. Flow cytometric analysis and colony assays were performed to assess the hematopoietic differentiation capacity of hiPSCs., Results: Here, we reveal human umbilical arterial endothelial cell-derived induced pluripotent stem cells (HuA-iPSCs) exhibit indistinguishable pluripotency in comparison with human embryonic stem cells and hiPSCs derived from other tissues of origin (umbilical vein endothelial cells, cord blood, foreskin fibroblasts, and fetal skin fibroblasts). However, HuA-iPSCs retain a transcriptional memory typical of the parental human umbilical cord arterial endothelial cells, together with a strikingly similar DNA methylation signature to umbilical cord blood-derived induced pluripotent stem cells that distinguishes them from other human pluripotent stem cells. Ultimately, HuA-iPSCs are most efficient in targeted differentiation toward hematopoietic lineage among all human pluripotent stem cells based on the functional and quantitative evaluation of both flow cytometric analysis and colony assays. Application of the Rho-kinase activator significantly reduces the effects of preferential hematopoietic differentiation in HuA-iPSCs, reflected in CD34
+ cell percentage of day 7, hematopoietic/endothelial-associated gene expression, and even colony-forming unit numbers., Conclusions: Collectively, our data suggest that somatic cell memory may predispose HuA-iPSCs to differentiate more amenably into hematopoietic fate, bringing us closer to generating hematopoietic cell types in vitro from nonhematopoietic tissue for therapeutic applications.- Published
- 2023
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199. The accumulation of miR-125b-5p is indispensable for efficient erythroblast enucleation.
- Author
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Fang F, Xu L, Liang L, Qu M, Yao H, Yue W, Chen L, Chen D, Fan Z, He L, Nan X, Zhang H, Xie X, and Pei X
- Subjects
- Mice, Animals, Caspase 3 genetics, Erythroblasts, Down-Regulation genetics, Proto-Oncogene Proteins c-bcl-2 genetics, MicroRNAs genetics
- Abstract
Erythroblast enucleation is a precisely regulated but not clearly understood process. Polycythemia shows pathological erythroblast enucleation, and we discovered a low miR-125b-5p level in terminal erythroblasts of patients with polycythemia vera (PV) compared to those of healthy controls. Exogenous upregulation of miR-125b-5p levels restored the enucleation rate to normal levels. Direct downregulation of miR-125b-5p in mouse erythroblasts simulated the enucleation issue found in patients with PV, and miR-125b-5p accumulation was found in enucleating erythroblasts, collectively suggesting the importance of miR-125b-5p accumulation for erythroblast enucleation. To elucidate the role of miR-125b-5p in enucleation, gain- and loss-of-function studies were performed. Overexpression of miR-125b-5p improved the enucleation of erythroleukemia cells and primary erythroblasts. Infused erythroblasts with higher levels of miR-125b-5p also exhibited accelerated enucleation. In contrast, miR-125b-5p inhibitors significantly suppressed erythrocyte enucleation. Intracellular imaging revealed that in addition to cytoskeletal assembly and nuclear condensation, miR-125b-5p overexpression resulted in mitochondrial reduction and depolarization. Real-time PCR, western blot analysis, luciferase reporter assays, small molecule inhibitor supplementation and gene rescue assays revealed that Bcl-2, as a direct target of miR-125b-5p, was one of the key mediators of miR-125b-5p during enucleation. Following suppression of Bcl-2, the activation of caspase-3 and subsequent activation of ROCK-1 resulted in cytoskeletal rearrangement and enucleation. In conclusion, this study is the first to reveal the pivotal role of miR-125b-5p in erythroblast enucleation., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
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200. Direct chemical reprogramming of human cord blood erythroblasts to induced megakaryocytes that produce platelets.
- Author
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Qin J, Zhang J, Jiang J, Zhang B, Li J, Lin X, Wang S, Zhu M, Fan Z, Lv Y, He L, Chen L, Yue W, Li Y, and Pei X
- Subjects
- Cell Differentiation, Erythroblasts, Fetal Blood, Humans, Blood Platelets, Megakaryocytes
- Abstract
Reprogramming somatic cells into megakaryocytes (MKs) would provide a promising source of platelets. However, using a pharmacological approach to generate human MKs from somatic cells remains an unmet challenge. Here, we report that a combination of four small molecules (4M) successfully converted human cord blood erythroblasts (EBs) into induced MKs (iMKs). The iMKs could produce proplatelets and release functional platelets, functionally resembling natural MKs. Reprogramming trajectory analysis revealed an efficient cell fate conversion of EBs into iMKs by 4M via the intermediate state of bipotent precursors. 4M induced chromatin remodeling and drove the transition of transcription factor (TF) regulatory network from key erythroid TFs to essential TFs for megakaryopoiesis, including FLI1 and MEIS1. These results demonstrate that the chemical reprogramming of cord blood EBs into iMKs provides a simple and efficient approach to generate MKs and platelets for clinical applications., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
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