Stem cells and development最新文献

{"title":"Acknowledgment of Reviewers 2024.","authors":"","doi":"10.1089/scd.2024.32589.revack","DOIUrl":"https://doi.org/10.1089/scd.2024.32589.revack","url":null,"abstract":"","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":"34 1-2","pages":"48"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conditional Immortalization Using SV40 Large T Antigen and Its Effects on Induced Pluripotent Stem Cell Differentiation Toward Retinal Progenitor Cells.","authors":"Qi Wang, Brittany N Allen, Laura R Bohrer, Erin R Burnight, Budd A Tucker, Kristan S Worthington","doi":"10.1089/scd.2024.0124","DOIUrl":"10.1089/scd.2024.0124","url":null,"abstract":"<p><p>Current treatments for retinal degenerative diseases are limited and cell replacement therapies, in tandem with a supportive biomaterial scaffold, serve as a promising emerging option. However, the development and in vitro testing of these therapies require large quantities of human retinal progenitor cells (RPCs) to thoroughly assess the impact of material properties, culture conditions, and surgical parameters on cell survival and fate to refine and optimize this approach. Although induced pluripotent stem cells (iPSCs) are an ideal cell source for human RPC derivation, large-scale production is resource-intensive and requires specialized expertise. In this study, our objective was to address this barrier by creating conditional, Tet-On SV40-T immortalized RPCs derived from human iPSCs. In our approach, we employ the Tet-On system to conditionally immortalize RPCs by inducing a SV40 large T (SV40-T) antigen, a gene known to influence cell cycle regulation and differentiation. We transduced human iPSCs with the Tet-On SV40-T system and analyzed their proliferation and RPC differentiation capabilities in the presence and absence of doxycycline (a tetracycline class of antibiotics). Our results revealed that while SV40-T immortalization increased cell proliferation, it adversely impacted the expression of crucial RPC markers (PAX6, SOX2, CHX10), leading to a significant loss of RPC identity and multipotency. This de-differentiation was irreversible, even after removing doxycycline, indicating permanent alterations in differentiation potential. Overall, this study highlights the challenges associated with generating and maintaining an immortal human RPC cell line, particularly with respect to balancing proliferation and differentiation. Our findings prompt further research into optimizing conditional immortalization techniques, culture conditions, and proliferation timing to maintain the integrity and functional characteristics of RPCs. Such advancements are crucial for reducing labor and costs associated with in vitro testing of therapeutics as we work toward the development of improved stem cell-based interventions for retinal disease.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"26-34"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single Cell Data Enables Dissecting Cell Types Present in Bulk Transcriptome Data.","authors":"Wasco Wruck, James Adjaye","doi":"10.1089/scd.2024.0152","DOIUrl":"10.1089/scd.2024.0152","url":null,"abstract":"<p><p>The quality of organoid models can be assessed by single-cell-RNA-sequencing (scRNA-seq) but often only bulk transcriptome data is available. Here we present a pipeline for the analysis of scRNA-seq data and subsequent \"deconvolution,\" which is a method for estimating cell type fractions in bulk transcriptome data based on expression profiles and cell types found in scRNA-seq data derived from biopsies. We applied this pipeline on bulk iPSC-derived kidney and brain organoid transcriptome data to identify cell types employing two scRNA-seq kidney datasets and one brain dataset. Relevant cells present in kidney (e.g., proximal tubules, distal convoluted tubules, and podocytes) and brain (e.g., neurons, astrocytes, oligodendrocytes, and microglia) with obligatory endothelial and immune-related cells were identified. We anticipate that this pipeline will also enable estimation of cell type fractions in organoids of other tissues.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"17-25"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wharton's Jelly Mesenchymal Stem Cells: Shaping the Future of Osteoarthritis Therapy with Advancements in Chitosan-Hyaluronic Acid Scaffolds.","authors":"Ahed Ghamrawi, Rasha Basso, Nour Shakik, Lara Haddad, Zeina Nasr, Chaza Harmouch","doi":"10.1089/scd.2024.0033","DOIUrl":"10.1089/scd.2024.0033","url":null,"abstract":"<p><p>This review explores the potential of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) in cartilage regeneration and osteoarthritis treatment. It covers key factors influencing chondrogenesis, including growth factors, cytokines, and hypoxia, focusing on precise timing. The effectiveness of three-dimensional cultures and scaffold-based strategies in chondrogenic differentiation is discussed. Specific biomaterials such as chitosan and hyaluronic acid are highlighted for tissue engineering. The document reviews clinical applications, incorporating evidence from animal research and early trials and molecular and histological assessments of chondrogenic differentiation processes. It addresses challenges and strategies for optimizing MSC-derived chondrocyte therapy, emphasizing the immunomodulatory properties of these cells. The review concludes as a comprehensive road map for future research and clinical applications in regenerative medicine.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Mesenchymal Stem Cell Encoded with Myogenic Gene for Treating Radiation-Induced Muscle Fibrosis.","authors":"In Gul Kim, So Young Eom, Hana Cho, Yewon Kim, Saeyeon Hwang, Hyunsoo Kim, Jungirl Seok, Seok Chung, Hye-Joung Kim, Eun-Jae Chung","doi":"10.1089/scd.2024.0073","DOIUrl":"10.1089/scd.2024.0073","url":null,"abstract":"<p><p>Radiation therapy (RT) is a typical treatment for head and neck cancers. However, prolonged irradiation of the esophagus can cause esophageal fibrosis due to increased reactive oxygen species and proinflammatory cytokines. The objective of this study was to determine whether myogenic gene-transfected mesenchymal stem cells (MSCs) could ameliorate damage to esophageal muscles in a mouse model of radiation-induced esophageal fibrosis. We cloned esophageal myogenic genes (MyoD, MyoG, and Myf6) using plasmid DNA. Afterward, myogenic genes were transfected into Human Mesenchymal Stem Cells (hMSCs) using electroporation. Gene transfer efficiency, stemness, and myogenic gene profile were examined using flow cytometry, quantitative polymerase chain reaction, and RNA sequencing. In vivo efficacy of gene-transfected hMSCs was demonstrated through histological and gene expression analyses using a radiation-induced esophageal fibrosis animal model. We have confirmed that the gene transfer efficiency was high (∼75%). Pluripotency levels in gene-transfected MSCs were significantly decreased compared with those in the control (vector). Particularly, myogenesis-related genes such as OAS2, OAS3, and HSPA1A were overexpressed in the group transfected with three genes. At 4 weeks after injection, it was found that thickness collagen layer and esophageal muscle in MSCs transfected with all three genes were significantly reduced compared to those in the saline group. Muscularis mucosa was observed prominently in the gene combination group. Moreover, expression levels of myogenin, Myf6, calponin, and SM22α known to be specific markers of esophageal muscles tended to increase in the group transfected with three genes. Therefore, using gene-transfected MSCs has the potential as a promising therapy against radiation-induced esophageal fibrosis.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"652-664"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Organoid Culture Technologies: Current Trends and Innovations.","authors":"Yanwei Ji, Yang Sun","doi":"10.1089/scd.2024.0132","DOIUrl":"10.1089/scd.2024.0132","url":null,"abstract":"<p><p>Organoids have emerged as valuable tools in investigating disease mechanisms, drug efficacy, and personalized medicine due to their capacity to recapitulate crucial aspects of tissue physiology, including cell-cell interactions, heterogeneity, microenvironmental cues, and drug responses. Despite their broad applicability across various research domains, conventional organoid culture methods are plagued by several limitations that hinder research progress. These limitations include the inability to faithfully recreate tissue microenvironments, immune contexts, and vascular systems. Fortunately, ongoing advancements in organoid culture techniques are addressing these shortcomings. In this review, we provide a comprehensive overview of current mainstream organoid culture protocols. By evaluating these protocols, researchers can identify the most suitable experimental methods, thereby optimizing resource allocation and experimental outcomes.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"631-644"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of Functioning Platelets from Mature Megakaryocytes Derived from CD34⁺ Umbilical Cord Blood Cells.","authors":"Zhiyong Zhong, Chuxin Chen, Ning Wang, Yaqi Qiu, Xiajing Li, Shoupei Liu, Haibin Wu, Xianglian Tang, Yingjie Fu, Qicong Chen, Tingting Guo, Yaming Wei, Yuyou Duan","doi":"10.1089/scd.2024.0095","DOIUrl":"10.1089/scd.2024.0095","url":null,"abstract":"<p><p>Clinically patients with thrombocytopenia are in urgent need of platelet transfusion, thus it is necessary to produce the platelets in large scale in vitro to meet the clinical needs. In this study, we developed efficient protocol to generate functioning platelets by differentiating umbilical cord blood (CB)-derived CD34⁺ cells into mature megakaryocytes. Under our condition, up to 85% of mature megakaryocytes were generated from CB-derived CD34⁺ cells, and over 75% CD42b⁺CD62p⁺ platelets were produced. The megakaryocytes at day 12 after the differentiation had the similar gene expression pattern to natural mature megakaryocytes, and AMPK and insulin signal pathway were activated to inhibit the apoptosis and benefit platelet release. There were up to 72% of the platelets that could bind with PAC1, which is the highest rate of CB CD34⁺ cell-derived platelets to play function <i>in vitro</i> to date. The recovery of hemostasis and coagulation was similar in thrombocytopenia mice injected with CB CD34⁺ cell-derived platelets and with human blood-derived platelets, respectively, and it is the first time to demonstrate that human CB CD34⁺ cell-derived platelets were functional <i>in vivo</i>. Therefore, our findings open a new avenue to provide an <i>in vitro</i> efficient approach to generate functional platelets for clinical applications.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"677-691"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of Periodontal Ligament Stem Cell-like Cells Derived from Feeder-Free Cultured Induced Pluripotent Stem Cells.","authors":"Daiki Yamashita, Sayuri Hamano, Daigaku Hasegawa, Hideki Sugii, Tomohiro Itoyama, Makoto Ikeya, Hidefumi Maeda","doi":"10.1089/scd.2024.0122","DOIUrl":"10.1089/scd.2024.0122","url":null,"abstract":"<p><p>The periodontal ligament (PDL) is a fibrous connective tissue that connects the cementum of the root to the alveolar bone. PDL stem cells (PDLSCs) contained in the PDL can differentiate into cementoblasts, osteoblasts, and PDL fibroblasts, with essential roles in periodontal tissue regeneration. Therefore, PDLSCs are expected to be useful in periodontal tissue regeneration therapy. In a previous study, we differentiated induced pluripotent stem cells (iPSCs) into PDLSC-like cells (iPDLSCs), which expressed PDL-related markers and mesenchymal stem cell (MSC) markers; they also exhibited high proliferation and multipotency. However, the iPSCs used in this differentiation method were cultured on mouse embryonic fibroblasts; thus, they constituted on-feeder iPSCs (OF-iPSCs). Considering the risk of contamination with feeder cell-derived components, iPDLSCs differentiated from OF-iPSCs (ie, OF-iPDLSCs) are unsuitable for clinical applications. In this study, we aimed to obtain PDLSC-like cells from feeder-free iPSCs (FF-iPSCs) using OF-iPDLSC differentiation method. First, we differentiated FF-iPSCs into neural crest cell-like cells (FF-iNCCs) and confirmed that FF-iNCCs expressed NCC markers (eg, Nestin and p75NTR). Then, we cultured FF-iNCCs on human primary PDL cell-derived extracellular matrix for 2 weeks; the resulting cells were named FF-iPDLSCs. FF-iPDLSCs exhibited higher expression of PDL-related and MSC markers compared with OF-iPDLSCs. FF-iPDLSCs also demonstrated proliferation and multipotency in vitro. Finally, we analyzed the ability of FF-iPDLSCs to form periodontal tissue in vivo upon subcutaneous transplantation with β-tricalcium phosphate scaffolds into dorsal tissues of immunodeficient mice. Eight weeks after transplantation, FF-iPDLSCs had formed osteocalcin-positive bone/cementum-like tissues and collagen 1-positive PDL-like fibers. These results suggested that we successfully obtained PDLSC-like cells from FF-iPSCs. Our findings will contribute to the development of novel periodontal regeneration therapies.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"665-676"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Potential Efficacy of Expanded Umbilical Cord-Derived Mesenchymal Stromal Cells in Luminal Ulcerative Colitis Patients.","authors":"Hanan Jafar, Dana Alqudah, Reem Rahmeh, Dana Al-Hattab, Khalid Ahmed, Rama Rayyan, Awni Abusneinah, Mohammad Rasheed, Yaser Rayyan, Abdalla Awidi","doi":"10.1089/scd.2024.0102","DOIUrl":"10.1089/scd.2024.0102","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is characterized by periods of flare-ups and remission. It is likely to be an autoimmune in origin, presenting persistent therapeutic challenges despite current therapies. This study aims to investigate the potential of umbilical cord mesenchymal stromal cells (UCMSCs) in treating ulcerative colitis (UC). This study is a prospective phase 1 pilot, open-label, single-arm, and single-center study. UCMSCs were cultured under current Good Manufacturing Practice (cGMP) conditions and intravenously administered to six patients with UC. Safety and efficacy were evaluated using the Mayo Score/Disease Activity Index. Among the six enrolled adult patients, five completed long-term follow-ups. All exhibited at diagnosis active UC confirmed through comprehensive assessment methods. Each patient received three injections intravenously 2 weeks apart with a dose of 100 million UCMSC each. No significant short-term or intermediate-term adverse events were detected post-UCMSC administration. Long-term follow-up at 12 and 24 months showed sustained safety and no adverse events. Notably, three out of five patients achieved a Mayo score of 0 for UC, maintained at both 12 and 24 months, indicating a highly significant response (<i>P</i> < 0.001). This study demonstrates the safety and potential efficacy of UCMSCs in active UC. However, larger trials are warranted to validate these preliminary findings and to establish the role of UCMSC therapy as an option for managing UC.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"645-651"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrapericardial Administration of Human Pericardial Fluid Cells Improves Cardiac Functions in Rats with Heart Failure.","authors":"Yaping Xu, Xiangli Zhang, Zhikun Fu, Yan Dong, Yuexin Yu, Yingtian Liu, Ziyu Liu, Jinfu Chen, Yao Yao, Yan Chen, Jer Ping Ooi, Bakiah Shaharuddin, Bin Yang, Jun Jie Tan, Zhikun Guo","doi":"10.1089/scd.2024.0072","DOIUrl":"10.1089/scd.2024.0072","url":null,"abstract":"<p><p>Heart failure (HF) is still the main cause of mortality worldwide. This study investigated the characteristics of human pericardial fluid-derived cells (hPFCs) and their effects in treating doxorubicin (DOX)-induced HF rats through intrapericardial injection. hPFCs were isolated from patients who underwent heart transplantation (<i>N</i> = 5). These cells that primarily expressed SCA-1, NANOG, and mesenchymal markers, CD90, CD105, and CD73, were able to form adipocytes, osteoblasts, and cardiomyocytes in vitro. Passage 3 hPFCs (2.5 × 10⁵ cells/heart) were injected into the pericardial cavity of the DOX-injured rat hearts, significantly improving cardiac functions after 4 weeks. The tracked and engrafted red fluorescent protein-tagged hPFCs coexpressed cardiac troponin T and connexin 43 after 4 weeks in the host myocardium. This observation was also coupled with a significant reduction in cardiac fibrosis following hPFC treatment <i>(P</i> < 0.0001 vs. untreated). The elevated inflammatory cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor-α in the DOX-treated hearts were found to be significantly reduced (<i>P</i> < 0.001 vs. untreated), while the regional proangiogenic vascular endothelial growth factor A (VEGFA) level was increased in the hPFC-treated group after 4 weeks (<i>P</i> < 0.05 vs. untreated). hPFCs possess stem cell characteristics and can improve the cardiac functions of DOX-induced HF rats after 4 weeks through pericardial administration. The improvements were attributed to a significant reduction in cardiac fibrosis, inflammation, and elevated regional proangiogenesis factor VEGFA, with evidence of cellular engraftment and differentiation in the host myocardium.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"616-629"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}