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The kidney is a complex organ with more than 20 types of specialized cells that play an important role in maintaining the body's homeostasis. The epithelial tubular cell is formed during embryonic development and has little proliferative capacity under physiological conditions, but after acute injury the kidney does have regenerative capacity. However, after repetitive or severe lesions, it may undergo a maladaptation process that predisposes it to chronic kidney injury. Regenerative medicine includes various repair and regeneration techniques, and these have gained increasing attention in the scientific literature. In the future, not only will these techniques contribute to the repair and regeneration of the human kidney, but probably also to the construction of an entire organ. New mechanisms studied for kidney regeneration and repair include circulating stem cells as mesenchymal stromal/stem cells and their paracrine mechanisms of action; renal progenitor stem cells; the leading role of tubular epithelial cells in the tubular repair process; the study of zebrafish larvae to understand the process of nephron development, kidney scaffold and its repopulation; and, finally, the development of organoids. This review elucidates where we are in terms of current scientific knowledge regarding these mechanisms and the promises of future scientific perspectives., Author(s): Fernanda T. Borges [sup.1] [sup.2] , Nestor Schor [sup.1] Author Affiliations: (Aff1) 0000 0001 0514 7202, grid.411249.b, Nephrology Division, Department of Medicine, Universidade Federal de São Paulo (UNIFESP), , [...]

Background Post-pneumonectomy bronchopleural fistulas (BPFs) are associated with high morbidity and mortality. Currently, since the management of BPFs is difficult to assess, the best therapeutic approach is prevention. Our objective was to evaluate the effects of adipose-derived stem cells (ASCs) on the healing of the bronchial stump in an experimental animal model. Methods Left pneumonectomy was performed in 37 Sprague-Dawley rats. Animals were randomly assigned to a control group (n = 13), an ASC group (n = 12), and an ASC plus Tissucol.sup.® group (ASCT) (n = 12). The ASCs and ASCTs were locally administered at the bronchial stump after surgical pneumonectomy. Animals were killed at 10 and 20 days. We analyzed histological changes and changes in the expression of relevant genes involved in wound repair in the bronchial stump. Results Two control animals, one animal from the ASC group, and one from the ASCT group died from early BPF. All the remaining animals had an adequate postoperative outcome. ASCs and ASCTs significantly decreased the necrosis and ulcerations of the bronchial stump at 10 and 20 days. ASCs significantly decreased mRNA expression of Igf1 at 10 days and Igf1, Tgfb1, Vegfa, and Col2a1 at 20 days, whereas there was increased expression of Agc1 and Col2a1 at 10 days and Sox6 at 20 days. Conclusions Our findings indicate that local ASCs protected the bronchial stump after pneumonectomy and induced local changes in gene expression related to their protective action. These results could lead to a potential new therapeutic modality for the prevention of BPF., Author(s): Pedro Llontop[sup.1] , Norberto Santana-Rodriguez[sup.1] [sup.2] , Bernardino Clavo[sup.1] [sup.3] , Ardiel Quintana[sup.1] , Maria D. Fiuza[sup.1] , Rafael Camacho[sup.4] , Alfredo Santana-Rodriguez[sup.1] , Carlos Santana[sup.5] , Jose A. [...]

Strategies to facilitate repair or generate new nephrons are exciting prospects for acute and chronic human renal disease. Repair of kidney injury involves not just local mechanisms but also mobilisation of progenitor/stem cells from intrarenal niches, including papillary, tubular and glomerular locations. Diverse markers characterise these unique cells, often including CD24 and CD133. Extrarenal stem cells may also contribute to repair, with proposed roles in secreting growth factors, transfer of microvesicles and exosomes and immune modulation. Creating new nephrons from stem cells is beginning to look feasible in mice in which kidneys can be dissociated into single cells and will then generate mature renal structures when recombined. The next step is to identify the correct human markers for progenitor cells from the fetus or mature kidney with similar potential to form new kidneys. Intriguingly, development can continue in vivo: whole foetal kidneys and recombined organs engraft, develop a blood supply and grow when xenotransplanted, and there are new advances in decellularised scaffolds to promote differentiation. This is an exciting time for human kidney repair and regeneration. Many of the approaches and techniques are in theirinfancyand based onanimal ratherthanhumanwork, but there is a rapid pace of discovery, and we predict that therapies based on advances in this field will come into clinical practice in the next decade. Keywords Nephrogenesis Stem cells * Kidney progenitor cells * Induced pluripotent stem(IPS) cells * Recombination culture * Acute renal injury * CKD5, Introduction Current treatments for end-stage kidney disease (chronic kidney disease stage 5; CKD5) are limited to dialysis or, if the patient is fortunate, renal transplantation. Quality of life (QOL) of [...]

Bone morphogenetic protein (BMP) signaling plays an essential role in many aspects of kidney development, and is a major determinant of outcome in kidney injury. BMP treatment is also an essential component of protocols for differentiation of nephron progenitors from pluripotent stem cells. This review discusses the role of BMP signaling to nephron progenitor cells in each of these contexts. Keywords Bone morphogenetic protein * BMP * Nephrogenesis * Nephron progenitor cell * Nephron differentiation * Renal repair * Embryonic stem cell differentiation, Embryonic nephron progenitor cells Over the course of approximately 10 days in the mouse and 30 weeks in the human, the permanent metanephric kidneys are endowed with their full complement [...]

Results from recent studies suggest that the beneficial effect of stem cell-based therapy is mainly dependent on a paracrine effect. The paracrine hypothesis implicates the ability of stem cells to limit injury or coordinate repair through the release of soluble factors. Among these factors microvesicles (MVs) have emerged as a mechanism through which stem cells may reprogram injured cells. In fact, MVs released from stem cells may deliver proteins, bio-active lipids and nucleic acids to injured cells. In particular, the transfer of transcripts derived from stem cells may induce phenotypic and functional changes in the recipient cells that promote the activation of regenerative programs. Keywords Exosomes * Microvesicles * Extracellular vesicles * Mesenchymal stem cells, Introduction Mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), are a heterogeneous multipotent cell population residing in the bone marrow that can be rapidly expanded in vitro while [...]

Abstract Many human diseases result from the (partial) loss of gene function. Once a disease-causing gene has been identified, a wide variety of techniques can be used to study its [...]

Byline: David Edgar (1,2), Simon Kenny (3), Sarah Almond (3), Patricia Murray (2) Keywords: Organogenesis; Topography; Stem cell; Development Abstract: The fundamental problem of development is to explain how the progeny of a single cell, the fertilised egg, differentiates to form all the tissues of the body in the right place at the right time. It has only been during the last couple of years that the mechanisms and molecules mediating interactions between cells and tissues have begun to be delineated. This article reviews some of these recent studies. Sequences of topoqraphically defined cellular interactions lead not only to the development of the body but also to the obvious and remarkable inference that the body more or less automatically builds itself. Author Affiliation: (1) Human Anatomy, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK (2) The University of Liverpool Department of Human Anatomy, Liverpool, UK (3) The University of Liverpool Department of Paediatric Surgery, Institute of Child Health, Alder Hey Children's Hospital, Liverpool, UK Article History: Registration Date: 21/09/2004 Accepted Date: 16/01/2004 Online Date: 28/10/2004

Byline: R. A. Musina (1), Ye. Ye. Yegorov (1), A. V. Belyavsky (1) Keywords: stem cells; pluripotency; differentiation; proliferative potential; plasticity; cell fusion; telomerase; cell therapy Abstract: The properties of some stem cells (SCs) that are most interesting in terms of their implications for medicine (embryonic, hematopoietic, and mesenchymal SCs) are considered. SCs are undifferentiated cells capable of both self-maintenance and differentiation into specialized cells. According to their origin, SCs are divided into embryonic and somatic ones. The former can be maintained in vitro for an infinitely long time and can differentiate into all cells of adult organisms. The latter have a limited capacity for differentiation and, probably, a limited proliferative potential. The plasticity of somatic SCs, i.e., their capacity for context-dependent differentiation into 'unrelated' cell types, is of considerable therapeutic importance, although some researchers doubt this capacity. It is assumed that most types of SCs differentiate by the stepwise hierarchical maturation mechanism, one of the steps being rapidly proliferating progenitor cells. The use of SCs in medicine is currently at the stage of preclinical trials. Although embryonic SCs are promising for medicine, there are serious limitations of their use in therapy in the near future. However, the first clinical trials have demonstrated that the approaches involving autotransplantation of hematopoietic and mesenchymal SCs are effective for treating ischemia of extremities and the consequences of myocardial infarction. Obviously, the use of SCs in medicine promises dramatic progress in treating many severe diseases. Author Affiliation: (1) Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia Article History: Registration Date: 26/09/2004

Byline: Dominik Parsch (1), Jorg Fellenberg (1), Tim H. Brummendorf (2), Anna-Maria Eschlbeck (1), Wiltrud Richter (1) Keywords: Telomere length; Telomerase activity; Mesenchymal stem cells; Chondrocytes; Aging Abstract: Chondrocyte ex vivo expansion currently performed to replace damaged articular surfaces is associated with a loss of telomeric repeats similar to decades of aging in vivo. This might affect the incidence or time of onset of age-related disorders within transplanted cells or tissues. This study examined whether more immature progenitor cells, such as mesenchymal stem cells (MSC), which can be expanded and subsequently differentiated into chondrocytes is advantageous regarding telomere-length related limitations of expansion protocols. Primary chondrocytes and bone-marrow-derived MSC were isolated from 12 donors, expanded separately to 4x10.sup.6 cells, and (re-)differentiated as three-dimensional chondrogenic spheroids. Cells were collected during expansion, after three-dimensional culturing and chondrogenic differentiation, and sequential analyses of telomere length and telomerase activity were performed. Surprisingly, telomeres of expanded MSC were significantly shorter than those from expanded chondrocytes from the same donor (11.4+-2.5 vs. 13.4+-2.2 kb) and tended to remain shorter after differentiation in chondrogenic spheroids (11.9+-1.8 vs. 13.0+- kb). While telomere lengths in native chondrocytes and MSC were not related to the age of the donor, significant negative correlations with age were observed in expanded (136 bp/year), three-dimensionally reconstituted (188 bp/year), and redifferentiated (229 bp/year) chondrocytes. Low levels of telomerase activity were found in MSC and chondrocytes during expansion and after (re-)differentiation to chondrogenic spheroids. In terms of replicative potential, as determined by telomere length, ex vivo expansion followed by chondrogenic differentiation of MSC did not provide a benefit compared to the expansion of adult chondrocytes. However, accelerated telomere shortening with age during expansion and redifferentiation argues for an 'age phenotype' in chondrocytes as opposed to MSC and suggests an advantage for the use of MSC especially in older individuals and protocols requiring extensive expansion Author Affiliation: (1) Department of Orthopedic Surgery, University of Heidelberg, Schlierbacher Landstrasse 200, 69118, Heidelberg, Germany (2) Department of Hematology and Oncology, University of Tubingen, Tubingen, Germany Article History: Registration Date: 23/10/2003 Received Date: 08/07/2003 Accepted Date: 14/10/2003 Online Date: 28/11/2003 Article note: D. Parsch and J. Fellenberg contributed equally to this manuscript

Byline: Yoshifumi Kato (1), Atsuyuki Yamataka (1), Katsumi Miyahara (2), Noriyoshi Sueyoshi (2), Jun Hayakawa (3), Mari Hayashida (3), Makoto Migita (3), Takashi Shimada (3), Hiroyuki Kobayashi (1), Geoffrey J. Lane (1), Takeshi Miyano (1) Keywords: Green fluorescence protein; Small intestine; Transplantation; Regeneration; Mesenchymal cell; Bone marrow cell Abstract: We examined whether non-hematopoietic BM cells can migrate into the intestinal graft after fetal small intestinal transplantation (FSITx). Fetal small intestine from donor C57BL/6 mice was transplanted into the rectus abdominis of recipient C57BL/6 mice with only green fluorescent protein (GFP) BM cells (syngeneic FSITx). Intestinal grafts were harvested on days 5, 10, and 30 after FSITx and stained immunohistochemically using anti-CD45 antibody (a marker for hematopoietic BM cells). Although there were no GFP-positive cells identified in the epithelium of the graft intestinal villi, there were a few cells positive for both GFP and CD45 in the lamina propria on day 5 after FSITx, and many present on days 10 and 30. In some grafts there were only cells that were GFP positive/CD45 negative (i.e., non-hematopoietic BM cells) found in the lamina propria on days 10 and 30. These data indicate that non-hematopoietic BM cells as well as hematopoietic BM cells can migrate from the recipient's bone marrow, suggesting that recipient mesenchymal stem cells may be strongly implicated in graft regeneration and development after FSITx. Author Affiliation: (1) Department of Pediatric Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-8421, Tokyo, Japan (2) Division of Pathology, Central Laboratory of Medical Sciences, Juntendo University School of Medicine, Tokyo, Japan (3) Departments of Pediatrics and Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan Article History: Registration Date: 01/01/2003 Online Date: 01/02/2004

Byline: Ivar Astby (1), Leiv S. Rusten (2), Gunnar Kvalheim (2), Per Grottum (1) Keywords: Granulopoiesis; Mathematical model; High dose chemotherapy; Stem cell support; Engraftment time; CFU-GM cells; CD34+ cells Abstract: High dose chemotherapy supported with hematopoietic progenitor cells gives a characteristic neutropenic period (blood neutrophils &lt 0.5a10.sup.9 c/l) ranging from 10 to 16 days. The question of a correlation between the CFU-GM content of the transplanted CD34+ cells and time to neutrophil recovery by patients having been given high-dose chemotherapy (HD-CT) with stem cell support was addressed by means of a mathematical model of granulopoiesis. The model utilizes a convection-reaction partial differential equation (PDE) with feedback from a cytokine compartment on proliferation, maturation, and mobilization of granulocytes from bone marrow to blood. The observed number of CFU-GM cells in the transplanted CD34+ cell autograft was used as input to the model. Using this approach, the observed gross relationship between CFU-GM content in the reinfused blood product and engraftment time could be reproduced. At the same time, the effects of assumed physiological mechanisms, especially some of the effects of G-CSF on proliferation rate, maturation rate, mobilization, and cell death, could be investigated and discussed relative to observed engraftment. The model makes it possible to explain how cytokines interfere with progenitor cell mobilization from bone marrow to blood, and it points out the implications of a regulating mechanism for the granulocyte maturation rate. Author Affiliation: (1) Department of Informatics, University of Oslo, 0316 Oslo, Norway (2) Stem Cell Laboratory, The Norwegian Radium Hospital, 0310 Oslo, Norway Article History: Received Date: 16/01/2001 Online Date: 23/04/2003

Byline: Tadashi Matsunaga (1), Fumiaki Sasaki (2), Mutsuro Ohira (2), Kohei Hashizume (2), Akira Hayashi (2), Yutaka Hayashi (2), Hideo Mugishima (2), Naomi Ohnuma (1) Keywords: Hepatoblastoma Lung metastasis Recurrence Stem cell transplantation Abstract: For better total survival rate of children with hepatoblastoma, the therapeutic strategy for recurrent or metastatic hepatoblastoma should be improved. From 1991 to 1999, 134 cases of hepatoblastoma were treated by surgery and combination chemotherapy of cisplatin (CDDP) and THP-Adriamycin (THP-ADR) based on the JPLT-1 protocol. In 114 non-metastatic cases, 90 primary liver tumors were resected completely by partial hepatectomy, but 12 recurrences were observed in the liver (4 cases) and the lungs (8 cases). Distant metastases on the diagnosis were observed in 20 cases. The treatment outcome of these 12 recurrent and 20 metastatic tumors was analyzed. In four recurrent liver tumors, surgical resection was performed in all four cases, and all the patients were alive and well. In eight recurrent lung tumors, surgical resection was performed completely in six cases with unilateral lung disease, and five of the six patients were alive and well. In stage IV tumors, the survival rate of the patients having primary tumors within two hepatic sections was significantly higher than that of the patients having primary tumors over three hepatic sections. Active surgical intervention to lung metastases and a more intensive chemotherapy to facilitate complete resection of primary hepatic tumor could improve survival rate of children with refractory hepatoblastoma. Author Affiliation: (1) Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan (2) , Japanese Study Group for Pediatric Liver Tumor (JPLT), Japan (3) Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, 260-8677, Chiba, Japan Article History: Accepted Date: 17/08/2002 Article note: Electronic Publication

Byline: E. Sidebotham (1), S. Kenny (1), D. Lloyd (1), C. Vaillant (2), D. Edgar (3) Keywords: Enteric nervous system Hirschsprung's disease Neural crest Stem cells Abstract: Hirschsprung disease is the result of aganglionosis of a variable length of the terminal bowel, which arises from the incomplete colonisation of the embryonic gut by vagal neural crest-derived cells (NCC) that migrate caudally from the pharyngeal gut to the rectum. We have previously shown that a very small group of NCC, at the leading edge of this wave of migration, can proliferate and differentiate to innervate the entire distal gut. It remains unknown if this capability is unique to those cells at the leading edge of NCC migration. The hypothesis tested was that NCC capable of acting as stem cells are found throughout the developing enteric nervous system (ENS). Gut was taken from mice at embryonic day 11.5 as the leading edge of NCC migration enters the colon. Terminal colon was separated as aganglionic recipient gut and its rostral end juxtaposed to the caudal end of the small intestine or caecum. The explants were cultured on nitrocellulose filters for up to 120 h, after which time the apposed segments had fused. The gut was then fixed and examined by immunohistochemistry to detect the neuronal markers PGP9.5 and nitric-oxide synthase (NOS) to assess development of enteric ganglia. NCC migrated from the proximal gut into the terminal colon, colonising it along its entire length. The pattern of NCC colonisation and differentiation of NOS-positive neurons was the same, regardless of whether the NCC were derived from the leading edge of migration in the caecum or from more proximal regions of the small intestine. Vagal NCC have the capacity to migrate into separated aganglionic terminal colon and differentiate into neurons. NCC at the leading edge of migration and those located more proximally within the gut demonstrate equivalent ability to migrate to and differentiate in the terminal rectum. Further studies are required to confirm which of these migrating NCC have the properties of ENS stem cells. Author Affiliation: (1) Department of Paediatric Surgery, Alder Hey Children's Hospital, Eaton Road, Liverpool, L12 2AP, UK (2) Department of Pre-Clinical Veterinary Science, University of Liverpool, Liverpool, UK (3) Department of Human Anatomy and Cell Biology, University of Liverpool, Liverpool, UK Article History: Accepted Date: 28/11/2001 Article note: Electronic Publication

Byline: A. P. Khrenov (1), L. N. Novikov (1), L. N. Novikova (1) Author Affiliation: (1) Department of Histology, Nizhnii Novgorod State Medical Academy, Russia Article History: Registration Date: 10/10/2004

Abstract An increasing number of patients suffer from chronic kidney disease (CKD). The progression of CKD is often relentless with the majority of patients reaching end-stage renal disease (ESRD) requiring [...]

Byline: Boon Chin Heng (1), Tong Cao (1) Author Affiliation: (1) Stem Cell Laboratory, Faculty of Dentistry, National University of Singapore, 5 Lower Kent Ridge Road, 119074, Singapore Article History: Registration Date: 08/07/2004 Received Date: 14/05/2004 Accepted Date: 15/06/2004 Online Date: 14/09/2004

Lesch-Nyhan disease (LND) is a monogenic rare neurodevelopmental disorder caused by a deficiency in hypoxanthine-guanine phosphoribosyltransferase (HPRT), the key enzyme of the purines salvage pathway. Beyond its well-documented metabolic consequences, HPRT deficiency leads to a distinctive neurobehavioral syndrome characterized by motor disabilities, cognitive deficits, and self-injurious behavior. Although various cell and animal models have been developed to investigate LND pathology, none have adequately elucidated the underlying mechanisms of its neurological alterations. Recent advances in human pluripotent stem cell research and in vitro differentiation techniques have ushered in a new era in rare neurodevelopmental disorders research. Pluripotent stem cells, with their ability to propagate indefinitely and to differentiate into virtually any cell type, offer a valuable alternative for modeling rare diseases, allowing for the detection of pathological events from the earliest stages of neuronal network development. Furthermore, the generation of patient-derived induced pluripotent stem cells using reprogramming technology provides an opportunity to develop a disease-relevant model within the context of a patient-specific genome. In this review, we examine current stem cell-based models of LND and assess their potential as optimal models for exploring key pathological molecular events during neurogenesis and for the discovering novel treatment options. We also address the limitations, challenges, and future prospects for improving the use of iPSCs in LND research., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Recent advances in neuroscience tools for single-cell molecular profiling of brain neurons have revealed an enormous spectrum of neuronal subpopulations within the neuroendocrine hypothalamus, highlighting the remarkable molecular and cellular heterogeneity of this brain area., Rationale: Neuronal diversity in the hypothalamus reflects the high functional plasticity of this brain area, where multiple neuronal populations flexibly integrate a variety of physiological outputs, including energy balance, stress and fertility, through crosstalk mechanisms with peripheral hormones. Intrinsic functional heterogeneity is also observed within classically 'defined' subpopulations of neuroendocrine neurons, including subtypes with distinct neurochemical signatures, spatial organisation and responsiveness to hormonal cues., Aim: The aim of this review is to critically evaluate past and current research on the functional diversity of hypothalamic neuroendocrine neurons and their plasticity. It focuses on how this neuronal plasticity in this brain area relates to metabolic control, feeding regulation and interactions with stress and fertility-related neural circuits., Conclusion: Our analysis provides an original framework for improving our understanding of the hypothalamic regulation of hormone function and the development of neuroendocrine diseases., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Prostate cancer (PCa) is one of the most common malignant tumors that exhibit both chemoresistance and recurrence. SUV39H2 is highly expressed in many types of human tumors, but its role in the development and progression of PCa has never been clarified. The aim of this study is to elucidate the role of SUV39H2 in the development and progression of PCa, its association with the AKT/FOXO signaling pathway, and its potential implications for PCa diagnosis and treatment. SUV39H2 expression was analyzed in The Cancer Genome Atlas (TCGA) and genotype tissue expression pan-cancer data. The TCGA database was evaluated for SUV39H2 enrichment and its correlation to immune cell infiltration. SUV39H2 levels in PCa tissues and control tissues were determined in 30 patients using qPCR and IHC. Clinical relevance was assessed via The Cancer Genome Atlas (TCGA). In vitro assessments including colony formation assays, Western Blot analysis, CCK-8 assays, and flow cytometry were utilized to establish SUV39H2's contribution to PCa cell growth. The influence of SUV39H2 on PC3 and DU145 cell proliferation was assessed through a cell line-derived xenograft model. Sphere formation assays and qPCR were employed to delineate SUV39H2's role in PCa stemness and chemosensitivity. In vitro macrophage polarization assays provided insights into SUV39H2's association with M2 macrophages, while enrichment analysis shed light on its role in FOXO signaling. PCa tissues expressed higher levels of SUV39H2 than normal tissues. By knocking down SUV39H2, PCa cells were made more chemosensitive to docetaxel and cell proliferation and stemness were inhibited. Additionally, SUV39H2 knockdown significantly inhibited in vivo PCa cell growth and inhibited the polarization of macrophages. Furthermore, SUV39H2 was found to regulate AKT/FOXO signaling by increasing Akt and FOXO3a phosphorylation. Our findings highlight SUV39H2's role in PCa cell apoptosis and chemosensitivity mainly by regulating the AKT/FOXO signaling pathway and suggest that SUV39H2 could be a potential target for PCa diagnosis and treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: 3D cancer stem cell (CSC) cultures are widely used as in vitro tumor models. In this study, we determined the effects of enriching HCT116 tumor spheres initially cultured in serum-free medium with different concentrations of serum, focusing on the effect of microserum environment stimulation on extraction and biological function of colorectal cancer stem cells (CCSCs)., Methods: CCSCs were enriched in standard serum-free medium and serum-free medium with different concentrations of serum for 1 week. The expression of CSC-associated markers in CCSCs, and the presence and relative proportion of CSCs (CD133/CD44 cell sorting) were then determined to elucidate the effect of the microserum environment on the preservation of CSC-related features. Further, the tumorigenic capacity of CCSCs was evaluated in an immunodeficiency mouse model., Results: Our data indicated that a significantly greater number of spheres with a greater size range and high viability without drastic alteration in biological and structural features, which maintained self-renewal potential after sequential passages were formed after serum supplementation. Real-time analysis showed that both serum spheres and serum-free spheres displayed similar expression patterns for key stemness genes. Serum spheres showed higher expression of the CSC surface markers CD133 and CD44 than did CSCs spheres cultured in serum-free medium. Adherent cultures in complete medium could adapt to the serum-containing microenvironment faster and showed higher proliferation ability. The addition of serum induced EMT and promoted the migration and invasion of serum globular cells. Compared with serum-free cells and adherent cells, serum spheres showed higher tumor initiation ability., Conclusions: Microserum environment stimulation could be an effective strategy for reliable enrichment of intact CCSCs, and a more efficient CSC enrichment method., (© 2023. Springer Science+Business Media, LLC.)

COVID-19 has severely devastated many lives across the globe. It has been speculated that stem cell-based therapy for COVID-19 treatment could be able to subsidize the effects. In preclinical and clinical studies, stem cell-based therapy has successfully eliminated inflammatory cytokines in ALI, ARDS, and COVID-19. Clinical trials have produced a variety of promising results for validating stem cell therapy in COVID-19 patients. For instance, exosome-based therapy (ExoFlow) showed an 87% survival status, and MSC-based therapy (Mesoblast) achieved an 83% survival rate in moderate to severe COVID-19 patients. This review debates the advantages of cell-free therapy, i.e., stem cell-derived exosome-based therapies, over stem cell-based therapy. This review aims to question whether the immunomodulatory effect of stem cells differs based on their origin and also tries to find possible answers for the best stem cells for treating SARS-CoV-2 infection. The role of stem cells and their extracellular vesicles in the upregulation of regulatory immune cells, growth factors (EGF, FGF, VEGF), and anti-inflammatory cytokines (IL-6, INF-α, galectin-1, notch-1, PDL-1) that promote the tissue regeneration at the injured site. The right side of the image depicts the downregulation of inflammation-inducing immune cells, pro-inflammatory cytokines, and chemokines that could also enhance COVID-19 therapy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Blood transfusions are now an essential part of modern medicine. Transfusable red blood cells (RBCs) are employed in various therapeutic strategies; however, the processes of blood donation, collection, and administration still involve many limitations. Notably, a lack of donors, the risk of transfusion-transmitted disease, and recent pandemics such as COVID-19 have prompted us to search for alternative therapeutics to replace this resource. Originally, RBC production was attempted via the ex vivo differentiation of stem cells. However, a more approachable and effective cell source is now required for broader applications. As a viable alternative, pluripotent stem cells have been actively used in recent research. In this review, we discuss the basic concepts related to erythropoiesis, as well as early research using hematopoietic stem cells ex vivo, and discuss the current trend of in vitro erythropoiesis using human-induced pluripotent stem cells., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Scaffolds engineered for in vitro tissue engineering consist of multiple pores where cells can migrate along with nutrient-rich culture medium. The presence of the nutrient medium throughout the scaffold pores promotes cell proliferation, and this process depends on several factors such as scaffold geometry, nutrient medium flow rate, shear stress, cell-scaffold focal adhesions and elastic properties of the scaffold material. While numerous studies have addressed the first four factors, the mathematical approach described herein focuses on cell proliferation rate in elastic scaffolds, under constant flux of nutrients. As cells proliferate, the scaffold pores radius shrinks and thus, in order to sustain the nutrient flux, the inlet applied pressure on the upstream side of the scaffold pore must be increased. This results in expansion of the elastic scaffold pore, which in turn further increases the rate of cell proliferation. Considering the elasticity of the scaffold, the pore deformation allows further cellular growth beyond that of inelastic conditions. In this paper, our objectives are as follows: (i) Develop a mathematical model for describing fluid dynamics, scaffold elasticity and cell proliferation for scaffolds consist of identical nearly cylindrical pores; (ii) Solve the models and then simulate cellular proliferation within an elastic pore. The simulation can emulate real life tissue growth in a scaffold and offer a solution which reduces the numerical burdens. Lastly, our results demonstrated are in qualitative agreement with experimental observations reported in the literature., (© 2023. The Author(s), under exclusive licence to Society for Mathematical Biology.)

This study aimed at investigating the relationship between concentrations of macro and trace elements in blood serum, and fluids from small and large follicles (SFF and LFF, respectively), oviduct (OF), and uterus (UF) of female dromedary camels. Fluids from small (2-6 mm) and large follicles (7-20 mm), oviduct and uterus, and blood samples were collected from 19 camels. The results indicated that the concentrations of serum Mg, Fe, and Mn were significantly higher than their follicular fluid, OF, and UF concentrations. Levels of Zn, Fe, Cu, Cr, and Mn were significantly higher in SFF than in LFF. Se and Mo concentrations were higher in LFF. Co concentration was lower in serum than in reproductive tract fluids. Cr concentration was higher in UF and OF than in the serum, SFF, and LFF. High Ca concentration was observed for serum and SFF, followed by LFF. The concentration of Na was about 1.18-fold higher in SFF than in serum, OF, and LFF, and approximately 4.1-fold higher in serum than in UF. K was present in higher concentration in SFF than in serum and LFF; however, its concentration was low in UF and OF. In conclusion, this study shows the concentrations of certain elements in small and large follicular, uterine, and oviductal fluids, which may be low or high depending on their function in the development and growth of follicles. This information can support the development of new media for in vitro oocyte maturation and fertilization of female camels.

The aim of our study was to explore psychological determinants of COVID-19 responsible behavior. We focused on trait anxiety and worry about the corona crisis, knowledge and unfounded beliefs about coronavirus and thinking dispositions (cognitive reflection, actively open-minded thinking, faith in intuition and science curiosity) that should drive knowledge and beliefs. Additionally, we tested the effectiveness of a one-shot intervention based on the 'consider counter-arguments' debiasing technique in changing COVID-19 unfounded beliefs. We used a convenience sample of 1439 participants who filled in the questionnaire on-line. Comparison of latent means showed that the 'consider counter-arguments' intervention did not affect unfounded beliefs. Structural equation model, conducted on 962 participants with data on all variables, indicated that greater worry and weaker endorsement of COVID-19 unfounded beliefs lead to more responsible COVID-19 behavior. The relationship of trait anxiety and thinking dispositions with the criterion was mediated through the worry about COVID-19 and unfounded beliefs about COVID-19, respectively., Author(s): Nikola Erceg [sup.1] , Mitja Ruzojcic [sup.1] , Zvonimir Galic [sup.1] Author Affiliations: (1) grid.4808.4, 0000 0001 0657 4636, Department of Psychology, Faculty of Humanities and Social Sciences, University [...]