Stem cells and development最新文献

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Alpha-Synuclein Inhibition Promotes Erythropoiesis by Affecting Methylation Modifications of Fructose and Mannose Metabolism.
Stem cells and development Pub Date : 2024-12-20 DOI: 10.1089/scd.2024.0160
Xinrong He, Zixiang Geng, Gang Zou, Zeyu Cui, Yu Wang, Jiamin Song, Jing Zhang, Yiye Shao, Jingtao Feng, Yuncheng Wu, Te Liu, Xiaoying Zhu
{"title":"Alpha-Synuclein Inhibition Promotes Erythropoiesis by Affecting Methylation Modifications of Fructose and Mannose Metabolism.","authors":"Xinrong He, Zixiang Geng, Gang Zou, Zeyu Cui, Yu Wang, Jiamin Song, Jing Zhang, Yiye Shao, Jingtao Feng, Yuncheng Wu, Te Liu, Xiaoying Zhu","doi":"10.1089/scd.2024.0160","DOIUrl":"https://doi.org/10.1089/scd.2024.0160","url":null,"abstract":"<p><p>Ninety-nine percent of alpha-synuclein (α-syn) in the human body is distributed in erythrocytes. However, the role that α-syn plays in erythropoiesis remains unclear. To determine the effect of α-syn on erythroid differentiation, the erythroid cells, derived from human CD34+ progenitors in the umbilical cord, were cultured in a system composed of a series of cytokines and harvested after 6 days. Our work showed α-syn inhibition-promoted erythropoiesis as characterized by altered activity of surface markers of erythroid development such as CD49d, CD36, and CD71; and different methylation status of GDP-D-mannose dehydratase, aldolase fructose-bisphosphate A, and sorbitol dehydrogenase, key enzymes involved in fructose and mannose metabolism. Reduced adenosine triphosphate and elevated lactic acid also suggested a shift in cellular metabolism from mitochondrial respiration to glycolysis. Our study revealed a previously unknown role for α-syn as a methylation regulator that alters the activity of key enzymes of the fructose and mannose metabolism, thus contributing to erythropoiesis.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866654","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}
引用次数: 0
An Optimized Method to Produce Human-Induced Pluripotent Stem Cell-Derived Limbal Stem Cells Easily Adaptable for Clinical Use. 制备人类诱导多能干细胞衍生瓣膜干细胞的优化方法,易于临床应用。
Stem cells and development Pub Date : 2024-12-17 DOI: 10.1089/scd.2024.0172
Michael J Edel, Helena Sarret Casellas, Jordi Requena Osete, Núria Nieto-Nicolau, Francisco Arnalich-Montiel, María P De Miguel, Samuel McLenachan, Danial Roshandel, Ricardo P Casaroli-Marano, Belén Alvarez-Palomo
{"title":"An Optimized Method to Produce Human-Induced Pluripotent Stem Cell-Derived Limbal Stem Cells Easily Adaptable for Clinical Use.","authors":"Michael J Edel, Helena Sarret Casellas, Jordi Requena Osete, Núria Nieto-Nicolau, Francisco Arnalich-Montiel, María P De Miguel, Samuel McLenachan, Danial Roshandel, Ricardo P Casaroli-Marano, Belén Alvarez-Palomo","doi":"10.1089/scd.2024.0172","DOIUrl":"https://doi.org/10.1089/scd.2024.0172","url":null,"abstract":"<p><p>In adults, the limbal stem cells (LSC) reside in the limbal region of the eye, at the junction of the cornea and the sclera where they renew the outer epithelial layer of the cornea assuring transparency. LSC deficiencies (LSCD) due to disease or injury account for one of the major causes of blindness. Among current treatments for LSCD, cornea transparency can be restored by providing new LSC to the damaged eye and induced pluripotent stem cells (iPSC) holds great promise as a new advanced cell source. A synthetic mRNA-based protocol to produce human iPSC from bone marrow mesenchymal stem cells has been defined. The results demonstrate a standardizable method that can be easily adaptable for clinical-grade production standards, produce high-purity LSC-like cells in a relatively rapid timeframe of 12 days, and can be successfully seeded on amniotic membrane or a biodegradable fibrin gel for transplantation. In vivo data demonstrated it is feasible to transplant the iPSC-LSC fibrin patch. In conclusion, an efficient method has been developed to produce patient-specific LSC and seed them on a scaffold fibrin gel for future treatment of LSC-deficiency disease.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848765","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}
引用次数: 0
Intermittent Fasting During Ramadan Increases the Absolute Number of Circulating Progenitor Stem Cells in Healthy Subjects.
Stem cells and development Pub Date : 2024-12-04 DOI: 10.1089/scd.2024.0194
Loubna Abdel Hadi, Samira Sheikh, Gisela M Suarez-Formigo, Aya Zakaria, Fatma Abdou, Carlos Agustin Villegas Valverde, Yendry Ventura Carmenate, Antonio Alfonso Bencomo-Hernandez, Rene Antonio Rivero-Jimenez
{"title":"Intermittent Fasting During Ramadan Increases the Absolute Number of Circulating Progenitor Stem Cells in Healthy Subjects.","authors":"Loubna Abdel Hadi, Samira Sheikh, Gisela M Suarez-Formigo, Aya Zakaria, Fatma Abdou, Carlos Agustin Villegas Valverde, Yendry Ventura Carmenate, Antonio Alfonso Bencomo-Hernandez, Rene Antonio Rivero-Jimenez","doi":"10.1089/scd.2024.0194","DOIUrl":"https://doi.org/10.1089/scd.2024.0194","url":null,"abstract":"<p><p>Fasting regimens have shown profound impact on pro-longevity and tissue regeneration in diverse species. Physiological events can induce a regenerative response in adult stem cells. However, little is known about signaling and activation of adult stem cells which are modulated by fasting. This study analyzed the presence of hematopoietic stem/progenitor cells (HSPCs) and their circulation in the peripheral blood (PB) of healthy male adults practicing Ramadan fasting. Ten healthy male volunteers were enrolled in this prospective observational study. PB samples were collected twice daily on days 0, 10, 20, and 30 of Ramadan fasting (RF). Populations of stem cells and serum soluble factors were analyzed by flow cytometry. As a response to RF, we report an increase in the average absolute count of circulating of HSPCs, defined as LIN<sup>-</sup>CD45<sup>-</sup> and LIN<sup>-</sup>CD45<sup>+</sup> cell subsets expressing the stem markers, CD34 and CD133. Changes in the number of HSPCs subsets reflected changes in the peripheral concentration of chemoattractant soluble factors during fasting. A chemotaxis assay showed a migratory property of HSPCs towards plasma, collected at D30 of fasting that contained a higher concentration of SCF and G-CSF. The relationship between RF and an increase in the number of circulating HSPCs in part, describes a regenerative response to the physiological changes during fasting and may open opportunities to define the role of dietary intervention in the stem cell therapy.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776044","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}
引用次数: 0
Development of Mesenchymal Stem Cell Encoded with Myogenic Gene for Treating Radiation-Induced Muscle Fibrosis. 开发具有致肌基因的间充质干细胞,用于治疗辐射引起的肌肉纤维化。
Stem cells and development Pub Date : 2024-12-01 Epub Date: 2024-10-08 DOI: 10.1089/scd.2024.0073
In Gul Kim, So Young Eom, Hana Cho, Yewon Kim, Saeyeon Hwang, Hyunsoo Kim, Jungirl Seok, Seok Chung, Hye-Joung Kim, Eun-Jae Chung
{"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}
引用次数: 0
Advancements in Organoid Culture Technologies: Current Trends and Innovations. 类器官培养技术的进步:当前趋势与创新。
Stem cells and development Pub Date : 2024-12-01 Epub Date: 2024-11-07 DOI: 10.1089/scd.2024.0132
Yanwei Ji, Yang Sun
{"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}
引用次数: 0
Generation of Functioning Platelets from Mature Megakaryocytes Derived from CD34+ Umbilical Cord Blood Cells. 从 CD34+ 脐带血细胞衍生的成熟巨核细胞生成功能性血小板。
Stem cells and development Pub Date : 2024-12-01 Epub Date: 2024-11-11 DOI: 10.1089/scd.2024.0095
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
{"title":"Generation of Functioning Platelets from Mature Megakaryocytes Derived from CD34<sup>+</sup> 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<sup>+</sup> cells into mature megakaryocytes. Under our condition, up to 85% of mature megakaryocytes were generated from CB-derived CD34<sup>+</sup> cells, and over 75% CD42b<sup>+</sup>CD62p<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> cell-derived platelets and with human blood-derived platelets, respectively, and it is the first time to demonstrate that human CB CD34<sup>+</sup> 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}
引用次数: 0
Establishment of Periodontal Ligament Stem Cell-like Cells Derived from Feeder-Free Cultured Induced Pluripotent Stem Cells. 从无喂养培养的诱导多能干细胞中建立牙周韧带干细胞样细胞
Stem cells and development Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI: 10.1089/scd.2024.0122
Daiki Yamashita, Sayuri Hamano, Daigaku Hasegawa, Hideki Sugii, Tomohiro Itoyama, Makoto Ikeya, Hidefumi Maeda
{"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}
引用次数: 0
Safety and Potential Efficacy of Expanded Umbilical Cord-Derived Mesenchymal Stromal Cells in Luminal Ulcerative Colitis Patients. 扩增脐带间充质基质细胞对腔隙性溃疡性结肠炎患者的安全性和潜在疗效
Stem cells and development Pub Date : 2024-12-01 Epub Date: 2024-10-24 DOI: 10.1089/scd.2024.0102
Hanan Jafar, Dana Alqudah, Reem Rahmeh, Dana Al-Hattab, Khalid Ahmed, Rama Rayyan, Awni Abusneinah, Mohammad Rasheed, Yaser Rayyan, Abdalla Awidi
{"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}
引用次数: 0
Conditional Immortalization Using SV40 Large T Antigen and Its Effects on Induced Pluripotent Stem Cell Differentiation Toward Retinal Progenitor Cells.
Stem cells and development Pub Date : 2024-11-29 DOI: 10.1089/scd.2024.0124
Qi Wang, Brittany N Allen, Laura R Bohrer, Erin R Burnight, Budd A Tucker, Kristan S Worthington
{"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":"https://doi.org/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":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752783","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}
引用次数: 0
Single Cell Data Enables Dissecting Cell Types Present in Bulk Transcriptome Data.
Stem cells and development Pub Date : 2024-11-29 DOI: 10.1089/scd.2024.0152
Wasco Wruck, James Adjaye
{"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":"https://doi.org/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":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","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}
引用次数: 0
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