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Annually, there are many bladder cancer patients undergoing radical cystectomy (RC) with urinary diversion worldwide. Until 2019, intestinal cystoplasty is still the gold standard for bladder replacement, but this therapy is always associated with severe complications. An ideal bladder substitute without using intestinal tissue remains a challenge today. In this work, an artificial mechatronics bladder (AMB) as a brand new bladder replacement approach is developed. We studied the main physiological function characteristics of a natural urinary bladder from teaching books and relevant papers. According to these characteristics, we completed an overall design of AMB and made a prototype in lab. The prototype successfully realized the functions of a natural bladder in vitro. It can expand to store urine in real time when urine is flowing into it. It can send a urination alarm when it is fully filled and can void urine automatically after receiving remote control signals. According to relevant papers and our test experience, if the prototype could be smaller and lighter and manufactured with good biocompatibility materials such as PTFE, we think it is possible for AMB to be implanted in an animal’s body, and we deduce AMB could realize the functions of a natural urinary bladder in vivo. After thorough validation from animal testing, we hope AMB can be a good clinical option for bladder removal patients in the future.

Early in gestation, wounds in fetal skin heal by regeneration, in which microRNAs play key roles. Seq-915_x4024 is a novel microRNA candidate confirmed by deep sequencing and mirTools 2.0. It is highly expressed in fetal keratinocytes during early gestation. Using an in vitro wound-healing assay, Transwell cell migration assay, and MTS proliferation assay, we demonstrated that keratinocytes overexpressing seq-915_x4024 exhibited higher proliferative activity and the ability to promote fibroblast migration and fibroblast proliferation. These characteristics of keratinocytes are the same biological behaviors as those of fetal keratinocytes, which contribute to skin regeneration. In addition, seq-915_x4024 suppressed the expression of the pro-inflammatory markers TNF-α, IL-6, and IL-8 and the pro-inflammatory chemokines CXCL1 and CXCL5. We also demonstrated that seq-915_x4024 regulates TGF-β isoforms and the extracellular matrix. Moreover, using an in vivo wound-healing model, we demonstrated that overexpression of seq-915_x4024 in keratinocytes suppresses inflammatory cell infiltration and scar formation. Using bioinformatics analyses, luciferase reporter assays, and western blotting, we further demonstrated that Sar1A, Smad2, TNF-α, and IL-8 are direct targets of seq-915_x4024. Furthermore, the expression of phosphorylated Smad2 and Smad3 was reduced by seq-915_x4024. Seq-915_x4024 could be used as an anti-fibrotic factor for the treatment of wound healing., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to evaluate the use of Insulin-Transferrin-Selenium (ITS) medium in place of fetal bovine serum (FBS) to culture human amnion mesenchymal stem cells (hAMSCs). Cell morphology, ultrastructure, proliferation, migration and MSC related markers were assessed accordingly. The hAMSCs were induced to osteocyte, chondrocyte, adipocyte and keratinocyte by culturing in appropriate induction medium. hAMSCs mRNA expression was detected for the matrix metalloproteinases 2 (MMP2), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), insulin-like growth factor-I (IGF-I), Platelet-derived Growth Factor (PDGF), and transforming growth factor beta 1 (TGF-β) by real-time quantitative RT-PCR. Our results showed that hAMSCs cultured in ITS medium exhibited similar proliferation rates, demonstrated a statistically significant increased migration and expressed similar levels of MSC markers(CD73+, CD90+, CD105+, CD45-, CD34-) compared with those cultured in FBS. Osteoblasts, chondrocytes, adipocytes and keratinocytes were differentiated. Results of transmission electron microscope (TEM) revealed that hAMSCs cultured in ITS medium underwent active metabolism. The mRNA expression of MMP2, VEGF, KGF, TGF-β, IGF-I and PDGF upregulated in ITS medium. In conclusion, ITS medium has the potential to be used for the expansion of hAMSCs before clinical application., (© 2019 by the Association of Clinical Scientists, Inc.)

Since the beginning of the use of stem cells in tissue regenerative medicine, there has been a search for optimal sources of stem cells. Human amniotic epithelial cells (hAECs) are derived from human amnions, which are typically discarded as medical waste, but were recently found to include cells with trilineage differentiation potential in vitro. Previous study has focused on the osteogenic differentiation ability of hAECs as seed cells in bone regeneration; however, their paracrine effects on osteoblasts (OBs) are yet to be elucidated. In the present study, conditioned medium (CM) derived from hAECs was used to determine their paracrine effects on the human fetal OB cell line (hFOB1.19), and the potential bioactive factors involved in this process were investigated. The results suggested that hAEC-CM markedly promoted the proliferation, migration and osteogenic differentiation of hFOB1.19 cells. Expression of transforming growth factor β1 (TGFβ1) and microRNA 34a-5p (miR-34a-5p) were detected in hAECs. Furthermore, it was demonstrated that TGFβ1 and miR-34a-5p stimulated the differentiation of hFOB1.19 cells, and that TGFβ1 promoted cell migration. Moreover, the effects of hAEC-CM were downregulated following the depletion of either TGFβ1 or miR-34a-5p. These results demonstrated that hAECs promote OB differentiation through the secretion of TGFβ1 and miR-34a-5p, and that hAECs may be an optimal cell source in bone regenerative medicine.

The repair strategy for the healing of skin wounds in fetuses differs from that in adults. Proliferation and migration of dermal fibroblasts are the main mechanisms associated with skin wound healing, as well as the complex interactions between epidermal keratinocytes (KCs) and dermal fibroblasts. In order to investigate the effects of fetal skin epidermal KCs on fetal and adult human dermal fibroblasts, KCs and fibroblasts were isolated from the skin tissue of mid‑gestational human fetuses and adults, and co‑cultured using a Transwell® system. When fetal mid‑gestational KCs were co‑cultured with either fetal or adult dermal fibroblasts, the proliferative and migratory potential of the fibroblasts was significantly enhanced. Furthermore, these phenotypic changes were concomitant with the upregulation of numerous proteins including mouse double minute 2 homolog, cyclin B1, phospho‑cyclin‑dependent kinase 1, phospho‑extracellular signal‑regulated kinase, and phospho‑AKT, along with C‑X‑C chemokine receptor 4, phospho‑p38 mitogen activated protein kinase, matrix metalloproteinase (MMP)‑2 and MMP‑9. Notably, no significant differences were observed between fetal and adult dermal fibroblasts in their responses to fetal mid‑gestational epidermal KCs, indicating that the cells from these two developmental stages respond in a similar manner to co‑culture with KCs.

Although transplantation of human mesenchymal stem cells (MSCs) derived from amnion (hAMSCs), bone marrow (hBMSCs) and adipose tissues (hADSCs) has been shown to aid in the repair of cutaneous wounds in mouse models, little information is available regarding the relative efficacy of MSCs from different sources. In this study, we compared their therapeutic potentials by transplanting equal numbers of hAMSCs, hBMSCs or hADSCs in a mouse model of cutaneous wounds. The results suggested that an hADSC injection has the most pronounced effect on wound closure. Histological evaluation showed enhanced re-epithelialization in the hADSC group compared with the hBMSC and hAMSC groups. Although there was a slight improvement in wound healing in the hAMSC and hBMSC groups, the differences between the groups were statistically insignificant. In a trans-well coculture model, wound healing migration and transwell migration assays showed that hADSCs were superior to hAMSCs and hBMSCs at promoting human dermal fibroblast (hDF) migration. However, there was no significant difference in fibroblast proliferation between the hAMSC, hBMSC and hADSC groups, as measured by WST assay. Our results also indicated that hDFs cocultured with hADSCs for 48 h significantly upregulated their mRNA expression of the cytokine vascular endothelial growth factor, basic fibroblast growth factor, keratinocyte growth factor and transforming growth factor-β and increased the mRNA and protein levels of type I collagen. Collectively, these data suggest that hADSCs are a potential source of MSCs for therapeutic healing in cutaneous wounds in terms of efficacy, accessibility and availability.