Stem cells and development最新文献

{"title":"Improvements in Gut Microbiota Dysbiosis in Aged Mice Transplanted with Adipose-Derived Stem Cells.","authors":"Zebiao Liu,&nbsp;Tao Wang,&nbsp;Yu Zhu,&nbsp;Hongxia Zhao,&nbsp;Zuping Zhou,&nbsp;Qiong Wu","doi":"10.1089/scd.2022.0257","DOIUrl":"https://doi.org/10.1089/scd.2022.0257","url":null,"abstract":"<p><p>Adipose-derived stem cells (ASCs), as a cell therapy with considerable therapeutic potential, have received increasing attention in tissue repair, endocrine regulation, immune regulation, and aging and obesity research. Gut microbiota are present in all organisms and play important roles in the development of aging and obesity. Dysbiosis activates inflammatory pathways that may contribute to the development of aging and obesity. We used C57BL/6 J mice of different ages to carry out the experiment. Young mice were used as donors for ASC. Feces from the three groups were collected for 16sRNA sequencing to analyze the species composition of intestinal microorganisms, and then, predicted metabolic pathways by PICRUSt2 using 16s rRNA gene sequences. Immune cell levels in abdominal adipose tissue were assessed by flow cytometry. The content of IL-6, IL-1β, TNF-α, and lipopolysaccharides in serum was measured by ELISA kit. Our 16sRNA sequencing data showed restoration of gut microbiota diversity and an increase in beneficial flora (Akkermansia, Lactobacillus, Prevotella) 7 days after ASC transplantation. In addition, the inflammatory environment improved in older transplanted mice.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9681737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Allogeneic Umbilical Cord Blood Therapy for Global Development Delay and Intellectual Disability.","authors":"Byoungwoo Cha,&nbsp;Hyunseok Kwak,&nbsp;Ji In Bang,&nbsp;Su Jin Jang,&nbsp;Mi Ri Suh,&nbsp;Jee In Choi,&nbsp;MinYoung Kim","doi":"10.1089/scd.2022.0252","DOIUrl":"https://doi.org/10.1089/scd.2022.0252","url":null,"abstract":"<p><p>Most pediatric patients with global developmental delay (GDD) or intellectual disability (ID) have disrupted development. Since allogeneic umbilical cord blood (UCB) may exert neurotrophic effects, a prospective clinical trial was conducted to assess the efficacy and safety of UCB therapy for GDD and ID. A total of 13 children (ages 23-149 months) with GDD and ID were enrolled and followed up for 12 months. Under criteria of histocompatibility and cell number, allogeneic UCB units were selected and infused once intravenously, and adverse events were monitored. The Bayley Scale of Infant Development-II (BSID-II) was used as primary outcome measurement tool, and evaluations for various functional abilities were also implemented. Safety assessment did not reveal significant adverse effects. Functional improvements in mental and motor developments along with daily living activities and languages were observed at 12 months postintervention compared with the baseline abilities (<i>P</i> < 0.05). Furthermore, mental developmental quotient derived from BSID-II mental scale revealed significantly facilitated improvement during the first 3 months (<i>P</i> < 0.05). In the survey conducted 80.7 ± 13.0 months after UCB infusion to assess satisfaction and long-term safety, no long-term adverse effects were reported, and 70% of the guardians reported satisfaction with the UCB infusion. Long-term changes in two patients who were regularly followed up beyond the study completion were noticeable. One case observed for 4 years showed dramatic improvement until 12 months after UCB therapy, whereas she showed insignificant improvement beyond 12 months after the therapy. Another case showed alleviation of autism with findings of anti-inflammatory response in his peripheral blood after UCB infusion. This clinical study provides support for further applications of UCB as a therapeutic avenue for children with GDD or ID owing to its safety and partial efficacy. Due to patient heterogeneity, further studies focusing on specific clinical manifestations and etiologies are required. Registered at www.clinicaltrials.gov (NCT01769716).</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9312116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Peritoneal Dialysis-Associated Peritoneal Injury.","authors":"Fang Yu,&nbsp;Jie Yang,&nbsp;Jia Chen,&nbsp;Xiaoyue Wang,&nbsp;Qingli Cai,&nbsp;Yani He,&nbsp;Kehong Chen","doi":"10.1089/scd.2022.0244","DOIUrl":"https://doi.org/10.1089/scd.2022.0244","url":null,"abstract":"<p><p>Peritoneal fibrosis is a critical sequela that limits the application of peritoneal dialysis (PD). This study explored the role and mechanism of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) in preventing PD-associated peritoneal injury. C57BL/6 mice were randomized into three groups: a control (saline), peritoneal injury [2.5% glucose peritoneal dialysate + lipopolysaccharide (LPS)], and peritoneal injury + exosome group. After 6 weeks, mice were dissected, and the parietal peritoneum was collected. The level of peritoneal structural and functional damage was assessed. Additionally, transcriptome analysis of the peritoneum and miRNA sequencing on BMSC-Exos were performed. The parietal peritoneum had significantly thickened, and peritoneal function was impaired in the peritoneal injury group. Peritoneal structural and functional damage was significantly reduced after exosome treatment, while peritoneal inflammation, fibrosis, angiogenesis, and mesothelial damage significantly increased. Transcriptomic analysis showed that the BMSC-Exos affected the cell cycle process, cell differentiation, and inflammatory response regulation. Significant pathways in the exosome group were enriched by inflammation, immune response, and cell differentiation, which constitute a molecular network that regulates the peritoneal protective mechanism. Additionally, inflammatory factors (TNF-α, IL-1β), fibrosis markers (α-SMA, collagen-III, fibronectin), profibrotic cytokines (TGF-β1), and angiogenesis-related factor (VEGF) were downregulated at the mRNA and protein levels through BMSC-Exos treatment. BMSC-Exos treatment can prevent peritoneal injury by inhibiting peritoneal fibrosis, inflammation, and angiogenesis, showing a multitarget regulatory effect. Therefore, BMSC-Exos therapy might be a new therapeutic strategy for treating peritoneal injury.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9305419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transamniotic Fetal Administration of Genetically Modified Hematopoietic Stem Cells Carrying a Human Transgene in a Syngeneic Rat Model.","authors":"Daniel F Labuz,&nbsp;Ashlyn E Whitlock,&nbsp;Ina Kycia,&nbsp;David Zurakowski,&nbsp;Dario O Fauza","doi":"10.1089/scd.2022.0222","DOIUrl":"https://doi.org/10.1089/scd.2022.0222","url":null,"abstract":"<p><p>Hematopoietic stem cell (HSC)-based gene therapy has already reached clinical reality in a few applications. Fetal administration of genetically modified HSCs has only been feasible to date through invasive and morbid methods. It has been recently shown that native donor HSCs can reach the fetal circulation and bone marrow after simple delivery into the amniotic fluid, at least in a syngeneic healthy model. We sought to determine whether the transamniotic route could also be a practical alternative for the fetal administration of genetically modified HSCs in a comparable model. Pregnant Lewis rat dams underwent volume-matched intra-amniotic injections in all their fetuses (<i>n</i> = 47) on gestational day 17 (E17; term = E21-22) of donor HSCs genetically modified using a custom lentiviral vector designed to constitutively express both a firefly luciferase reporter gene and a human adenosine deaminase (ADA) transgene. Donor HSCs consisted of syngeneic cells isolated from the amniotic fluid and phenotyped by flow cytometry. Fetuses were euthanized at term, when seven select sites relevant to HSC-based therapies were screened for either luciferase activity by luminometry or for the presence of human ADA mRNA by digital droplet polymerase chain reaction (ddPCR). Among survivors (30/47; 64%), positive luminescence and positive human ADA expression were detected in the bone marrow (respectively, 33% and 76%), liver (respectively, 11% and 81%), spleen (respectively, 11% and 67%), thymus (respectively, 33% and 67%), lungs (respectively, 44% and 86%), and brain (respectively, 22% and 90%). Nucleated peripheral blood cells were analyzed only by ddPCR, showing positive human ADA expression at 54%. We conclude that genetically modified HSCs can reach the fetal circulation and fetal bone marrow after simple intra-amniotic administration in a syngeneic rat model. Gene therapy by transamniotic HSC delivery may become a practicable, minimally invasive strategy for the prenatal treatment of select hemoglobinopathies, immunodeficiencies, and inherited metabolic disorders.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9667541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Therapies: Yesterday, Today, and Tomorrow.","authors":"Hector Mayani","doi":"10.1089/scd.2022.0294","DOIUrl":"https://doi.org/10.1089/scd.2022.0294","url":null,"abstract":"<p><p>Cellular therapy (CT) can be defined as the transference into a person of healthy cells to correct defective functions. <i>Yesterday</i> (1950-2010), CT consisted mostly of hematopoietic transplants for the treatment of a variety of hematological disorders. Interestingly, during that period of time other cell types with therapeutic potential-including certain lymphoid populations and other nonhematopoietic cells-were discovered and characterized; thus, CT became a promising discipline for the treatment of a broader diversity of diseases. <i>Today</i> (2011-2023), CT has significantly grownup through preclinical studies and clinical trials, and it is currently progressing toward its consolidation as one of the pillars of medicine in the 21st century. Indeed, different types of stem cells (e.g., hematopoietic, mesenchymal, neural, and pluripotent), as well as different lymphoid and myeloid cell populations (e.g., TILs, CAR-Ts, CAR-NKs, and DUOC-01) are being used in clinical settings or are being tested in clinical trials. For the past decade, several CT modalities have been developed, and today, many of them are being used in the clinic. <i>Tomorrow</i> (2024-2040), already established CT modalities will surely be improved and applied more frequently, and novel therapies (that will include cell types such as iPSCs) will enter and expand within the clinical ground. It is noteworthy, however, that despite significant advancements and achievements, problems still need to be solved and obstacles need to be overcome. Technical, ethical, and economic issues persist and they need to be addressed. Undoubtedly, exciting times of challenges and opportunities are coming ahead in the CT arena.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9317828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Oogonial Stem Cells in Adult Mouse Ovaries with Age and Comparison to In Silico Data on Human Ovarian Aging.","authors":"Julie A MacDonald,&nbsp;Hannah C Sheehan,&nbsp;Andrew Piasecki,&nbsp;Luciana R Faustino,&nbsp;Charlotte Hauschildt,&nbsp;Victor Stolzenbach,&nbsp;Dori C Woods,&nbsp;Jonathan L Tilly","doi":"10.1089/scd.2022.0284","DOIUrl":"https://doi.org/10.1089/scd.2022.0284","url":null,"abstract":"<p><p>Many adult somatic stem cell lineages are comprised of subpopulations that differ in gene expression, mitotic activity, and differentiation status. In this study, we explored if cellular heterogeneity also exists within oogonial stem cells (OSCs), and how chronological aging impacts OSCs. In OSCs isolated from mouse ovaries by flow cytometry and established in culture, we identified subpopulations of OSCs that could be separated based on differential expression of stage-specific embryonic antigen 1 (SSEA1) and cluster of differentiation 61 (CD61). Levels of aldehyde dehydrogenase (ALDH) activity were inversely related to OSC differentiation, whereas commitment of OSCs to differentiation through transcriptional activation of <i>stimulated by retinoic acid gene 8</i> was marked by a decline in ALDH activity and in SSEA1 expression. Analysis of OSCs freshly isolated from ovaries of mice between 3 and 20 months of age revealed that these subpopulations were present and persisted throughout adult life. However, expression of <i>developmental pluripotency associated 3</i> (<i>Dppa3</i>), an epigenetic modifier that promotes OSC differentiation into oocytes, was lost as the mice transitioned from a time of reproductive compromise (10 months) to reproductive failure (15 months). Further analysis showed that OSCs from aged females could be established in culture, and that once established the cultured cells reactivated <i>Dppa3</i> expression and the capacity for oogenesis. Analysis of single-nucleus RNA sequence data sets generated from ovaries of women in their 20s versus those in their late 40s to early 50s showed that the frequency of <i>DPPA3</i>-expressing cells decreased with advancing age, and this was paralleled by reduced expression of several key meiotic differentiation genes. These data support the existence of OSC subpopulations that differ in gene expression profiles and differentiation status. In addition, an age-related decrease in <i>Dppa3</i>/<i>DPPA3</i> expression, which is conserved between mice and humans, may play a role in loss of the ability of OSCs to maintain oogenesis with age.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9189358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPK Regulates DNA Methylation of PGC-1α and Myogenic Differentiation in Human Mesenchymal Stem Cells.","authors":"Jianbo Wu, Shelly Gulati, April M Teague, Youngsil Kim, Jeanie B Tryggestad, Shaoning Jiang","doi":"10.1089/scd.2022.0226","DOIUrl":"10.1089/scd.2022.0226","url":null,"abstract":"<p><p>Adverse intrauterine environments can cause persistent changes in epigenetic profiles of stem cells, increasing susceptibility of the offspring to developing metabolic diseases later in life. Effective approaches to restore the epigenetic landscape and function of stem cells remain to be determined. In this study, we investigated the effects of pharmaceutical activation of AMP-activated protein kinase (AMPK), an essential regulator of energy metabolism, on mitochondrial programming of Wharton's Jelly mesenchymal stem cells (WJ-MSCs) from women with diabetes during pregnancy. Induction of myogenic differentiation of WJ-MSCs was associated with increased proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression and mitochondrial DNA (mtDNA) abundance. Inhibition of DNA methylation by 5 Azacytidine significantly increased PGC-1α expression and mtDNA abundance in WJ-MSCs, which were abolished by AMPK inhibitor Compound C (CC), suggesting an AMPK-dependent role of DNA demethylation in regulating mitochondrial biogenesis in WJ-MSCs. Furthermore, activation of AMPK in diabetic WJ-MSCs by AICAR or metformin decreased the level of PGC-1α promoter methylation and increased PGC-1α expression. Notably, decreased PGC-1α promoter methylation by transient treatment of AMPK activators persisted after myogenic differentiation. This was associated with enhanced myogenic differentiation capacity of human WJ-MSCs and increased mitochondrial function. Taken together, our findings revealed an important role for AMPK activators in epigenetic regulation of mitochondrial biogenesis and myogenesis in WJ-MSCs, which could lead to potential therapeutics for preventing fetal mitochondrial programming and long-term adverse outcome in offspring of women with diabetes during pregnancy.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9189359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YTHDF1 Enhances Chondrogenic Differentiation by Activating the Wnt/β-Catenin Signaling Pathway.","authors":"Xiaoming Yang,&nbsp;Youxi Lin,&nbsp;Taiqiu Chen,&nbsp;Wenjun Hu,&nbsp;Pengfei Li,&nbsp;Xuemei Qiu,&nbsp;Bo Yang,&nbsp;Anjing Liang,&nbsp;Wenjie Gao","doi":"10.1089/scd.2022.0216","DOIUrl":"https://doi.org/10.1089/scd.2022.0216","url":null,"abstract":"<p><p>Cartilage is derived from the chondrogenic differentiation of stem cells, for which the regulatory mechanism has not been fully elucidated. N6-methyladenosine (m6A) messenger RNA (mRNA) methylation is the most common posttranscriptional modification in eukaryotic mRNAs and is mediated by m6A regulators. However, whether m6A regulators play roles in chondrogenic differentiation is unknown. Herein, we aim to determine the role of a main m6A reader protein, YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), in chondrogenic differentiation regulation. Western blotting (WB) assays found that the expression of YTHDF1 increased during chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The results of quantitative polymerase chain reaction, WB, immunohistochemistry, and Alcian blue staining revealed that overexpression of YTHDF1 increased cartilage matrix synthesis and the expression of chondrogenic markers when hBMSCs, ATDC5 cells, or C3H10T1/2 cells were induced to undergo chondrogenesis. Conversely, chondrogenesis was clearly inhibited when YTHDF1 was knocked down in hBMSCs, ATDC5 cells, or C3H10T1/2 cells. Further RNA sequencing and molecular biology experiments found that YTHDF1 activated the Wnt/β-catenin signaling pathway during chondrogenic differentiation. Finally, the effects of overexpression and knockdown of YTHDF1 on chondrogenic differentiation were reversed by inhibiting or activating β-catenin activity. Therefore, we demonstrated that YTDHF1 promoted chondrogenic differentiation through activation of the Wnt/β-catenin signaling pathway.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9181392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Differences in the Role of Ductal Stem Cells in Mouse Major Salivary Glands.","authors":"Raksha Narendra, Ninche Ninche, Soosan Ghazizadeh","doi":"10.1089/scd.2022.0266","DOIUrl":"10.1089/scd.2022.0266","url":null,"abstract":"<p><p>Salivary gland (SG) stem cells are the only cell population capable of extended growth in organotypic cultures, and thus they are considered a source for cell-based therapies aimed at SG regeneration. Studies in the mouse submandibular gland have identified only one population of tissue stem cells capable of salisphere formation in culture. These cells are actively dividing ductal cells that express epithelial progenitor markers keratin (K) 5/14 and normally function as lineage-restricted stem cells for differentiated ductal cells. In response to severe injury, however, these cells undergo a multipotency switch and contribute to regeneration of multiple cell lineages, including secretory units or acini. Little is known about the mechanism of cell renewal and regeneration in the other major SGs and whether comparable stem cell populations exist in the parotid (PG) and sublingual (SLG) glands. Using in vivo and ex vivo models, we show that both the PG and SLG contain a small population of K14-expressing ductal cells. Although they do not cycle frequently, K14-expressing ductal cells are the source of salisphere-forming cells in these glands. Long-term lineage tracing studies in adult mouse PGs showed a progenitor-progeny relationship between the K14-expressing ductal cells and the K19-expressing ductal cells in the striated ducts. In the SLGs, however, K14-expressing ductal cells did not generate a differentiated cell progeny for a 6-month period of observation and did not make a significant contribution to regeneration of gland after severe injury. These studies reveal the functional similarities and differences in tissue stem cells among the major SGs and have implications for developing strategies for SG regenerative therapies.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9534546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Stem Cell Niche-Related Biomarkers at the Base of the Human Tricuspid Valve.","authors":"Jacob Sjölin,&nbsp;Marianne Jonsson,&nbsp;Charlotta Orback,&nbsp;Anders Oldfors,&nbsp;Anders Jeppsson,&nbsp;Jane Synnergren,&nbsp;Victoria Rotter Sopasakis,&nbsp;Kristina Vukusic","doi":"10.1089/scd.2022.0253","DOIUrl":"https://doi.org/10.1089/scd.2022.0253","url":null,"abstract":"<p><p>Stem cell niches have been thoroughly investigated in tissue with high regenerative capacity but not in tissues where cell turnover is slow, such as the human heart. The left AtrioVentricular junction (AVj), the base of the mitral valve, has previously been proposed as a niche region for cardiac progenitors in the adult human heart. In the present study, we explore the right side of the human heart, the base of the tricuspid valve, to investigate the potential of this region as a progenitor niche. Paired biopsies from explanted human hearts were collected from multi-organ donors (<i>N</i> = 12). The lateral side of the AVj, right atria (RA), and right ventricle (RV) were compared for the expression of stem cell niche-related biomarkers using RNA sequencing. Gene expression data indicated upregulation of genes related to embryonic development and extracellular matrix (ECM) composition in the proposed niche region, that is, the AVj. In addition, immunohistochemistry showed high expression of the fetal cardiac markers MDR1, SSEA4, and WT1 within the same region. Nuclear expression of HIF1α was detected suggesting hypoxia. Rare cells were found with the co-staining of the proliferation marker PCNA and Ki67 with cardiomyocyte nuclei marker PCM1 and cardiac Troponin T (cTnT), indicating proliferation of small cardiomyocytes. WT1+/cTnT+ and SSEA4+/cTnT+ cells were also found, suggesting cardiomyocyte-specific progenitors. The expression of the stem cell markers gradually decreased with distance from the tricuspid valve. No expression of these markers was observed in the RV tissue. In summary, the base of the tricuspid valve is an ECM-rich region containing cells with expression of several stem cell niche-associated markers. Co-expression of stem cell markers with cTnT indicates cardiomyocyte-specific progenitors. We previously reported similar data from the base of the mitral valve and thus propose that human adult cardiomyocyte progenitors reside around both atrioventricular valves.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9615394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}