Stem cells and development最新文献

{"title":"Epithelial-Mesenchymal Transition Functions as a Driver for the Direct Conversion of Somatic Cells.","authors":"Tsutomu Motohashi, Hitomi Aoki, Takahiro Kunisada, Masatake Osawa","doi":"10.1089/scd.2024.0181","DOIUrl":"10.1089/scd.2024.0181","url":null,"abstract":"<p><p>Direct conversion is an innovative new technology that involves the conversion of somatic cells to target cells without passing through a pluripotent state. Forced expression alone or in combination with transcription factors (TFs), which are critical for the generation of target cells, is important for successful direct conversion. However, most somatic cells are unable to directly convert into target cells even with forced expression. We herein demonstrated that epithelial-mesenchymal transition (EMT) is advantageous for the direct conversion of somatic cells. We previously reported that mouse keratinocytes converted into neural crest cells (NCCs) following the forced expression of the NCC specifier Sox10 in combination with expression of the TFs Snail1, Slug, Twist1, and Tcfap2a (4 TFs). 4 TFs induced EMT in keratinocytes; therefore, EMT was considered to be advantageous for direct conversion. The direct conversion of mouse mammary gland epithelial cells (NMuMG cells) into NCCs was not observed with the forced expression of Sox10, but was detected with the expression of Sox10 following the induction of EMT by 4 TFs. Furthermore, TGF-β1-induced EMT and Sox10 expression directly converted NMuMG cells into NCCs. These results suggest that the induction of EMT in somatic cells is advantageous for direct conversion.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"117-126"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019303","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":"Muse Cells Orchestrating Renal Repair via Macrophage M2 Polarization in Ischemia-Reperfusion Injury.","authors":"Shengyi Wang, Yutong Liu, Shenglei Zhang, Peng Wang","doi":"10.1089/scd.2024.0209","DOIUrl":"10.1089/scd.2024.0209","url":null,"abstract":"<p><p>Acute renal ischemia-reperfusion injury (IRI) poses significant challenges in clinical management, necessitating the exploration of novel therapeutic strategies. This study investigates the therapeutic potential and underlying mechanisms of multilineage-differentiating stress-enduring (Muse) cells in alleviating renal IRI. In recent years, stem cell research has advanced significantly, providing promising prospects for clinical treatment. Mesenchymal stromal cells (MSCs), from which Muse cells are derived, are a heterogeneous population of cells that include stem cells with varying degrees of multipotency, committed progenitors, and differentiated cells. Muse cells, a subpopulation of MSCs, were isolated from adipose tissue obtained through liposuction in this study. In vivo studies revealed the effective recruitment of Muse cells to injured kidneys and their ability to ameliorate renal pathological damage and improve renal function in a rat model of acute kidney IRI. Mechanistically, Muse cells modulated the polarization of macrophages toward an anti-inflammatory M2 phenotype, as evidenced by decreased M1/M2 ratios. In vitro experiments further elucidated the interaction between Muse cells and macrophages, demonstrating Muse cell-mediated promotion of M2 polarization. Co-culture with M2 macrophages during reoxygenation phases enhanced the survival of renal tubular epithelial cells following hypoxia-reoxygenation injury, highlighting the therapeutic potential of Muse cells in mitigating renal IRI through modulation of macrophage polarization. These findings provide insights into the therapeutic mechanisms of Muse cells and offer promising avenues for the development of innovative renal injury treatments.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"136-147"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401127","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":"Exploring the Potential of Stem Cells in Modulating Gut Microbiota and Managing Hypertension.","authors":"Asma Ismail Mahmod, Kayatri Govindaraju, Yogeswaran Lokanathan, Nur Akmarina B M Said, Baharudin Ibrahim","doi":"10.1089/scd.2024.0195","DOIUrl":"10.1089/scd.2024.0195","url":null,"abstract":"<p><p>Hypertension, commonly known as high blood pressure, is a significant health issue that increases the risk of cardiovascular diseases, stroke, and renal failure. This condition broadly encompasses both primary and secondary forms. Despite extensive research, the underlying mechanisms of systemic arterial hypertension-particularly primary hypertension, which has no identifiable cause and is affected by genetic and lifestyle agents-remain complex and not fully understood. Recent studies indicate that an imbalance in gut microbiota, referred to as dysbiosis, may promote hypertension, affecting blood pressure regulation through metabolites such as short-chain fatty acids and trimethylamine N-oxide. Current antihypertensive medications face limitations, including resistance and adherence issues, highlighting the need for novel therapeutic approaches. Stem cell therapy, an emerging field in regenerative medicine, shows promise in addressing these challenges. Stem cells, with mesenchymal stem cells being a prime example, have regenerative, anti-inflammatory, and immunomodulatory properties. Emerging research indicates that stem cells can modulate gut microbiota, reduce inflammation, and improve vascular health, potentially aiding in blood pressure management. Research has shown the positive impact of stem cells on gut microbiota in various disorders, suggesting their potential therapeutic role in treating hypertension. This review synthesizes the recent studies on the complex interactions between gut microbiota, stem cells, and systemic arterial hypertension. By offering a thorough analysis of the current literature, it highlights key insights, uncovers critical gaps, and identifies emerging trends that will inform and guide future investigations in this rapidly advancing field.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"99-116"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019306","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":"Developing a Serum-Free and Cytokine-Optimizing Induction Medium to Increase the Production of CD14⁺CD16⁺ and CD14⁺CD16^- Monocytes from Human CD133⁺ Hematopoietic Stem and Progenitor Cells.","authors":"Tsung-Yu Tseng, Yi-Ting Lai, Yun Chen, Hsing-Fen Tsai, Keng-Fu Hsu, Shu-Ching Hsu, Chao-Ling Yao","doi":"10.1089/scd.2024.0143","DOIUrl":"10.1089/scd.2024.0143","url":null,"abstract":"<p><p>Immunotherapy utilizes immune cells to target cancer and improves treatment outcomes with few side effects. Despite the effectiveness of immunotherapy, the limited availability of monocytes, which are essential for the differentiation of antigen-presenting cells, remains a major challenge. In this study, we developed a technique for inducing monocytes from hematopoietic stem and progenitor cells by using a serum-free (SF) medium supplemented with optimal concentrations of serum substitutes and cytokines. Three key serum substitutes, namely lipids, ascorbic acid, and β-glycerophosphate, were identified through factorial design screening, with their concentrations optimized through steepest ascent path analysis. Iscove's modified Dulbecco's medium was identified as the optimal basal medium. Long-term culturing confirmed the successful induction of CD14⁺CD16⁺ and CD14⁺CD16^- monocytes. Functional assays validated the efficacy of this technique with comparable gene expression, cytokine secretion, phagocytosis ability, and T-cell stimulating ability between SF and serum-containing cultures. Under SF conditions, high expression levels of CD16 were detected, indicating the broad range of potential applications of CD16⁺ monocytes. Overall, this technique represents a feasible SF alternative for monocyte generation, with potential benefits for immunotherapy.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"73-84"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916717","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":"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":"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":"85-98"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","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}

{"title":"PEGylated Granulocyte Colony-Stimulating Factor and Plerixafor Enhance Autologous Stem and Progenitor Cell Mobilization and Transplantation in Pediatric Patients.","authors":"Caroline Hochheuser, Maria L Rozeman, Nina Kunze, Nina U Gelineau, Carlijn Kuijk, Antoinette Jaspers-Bakker, Cor van den Bos, Miranda P Dierselhuis, Tirza J E Slager, Marta Fiocco, József Zsiros, Wim J E Tissing, Kasper Westinga, Christian M Zwaan, Carlijn Voermans, Godelieve A M Tytgat, Kathelijne C J M Kraal, Ilse Timmerman","doi":"10.1089/scd.2024.0178","DOIUrl":"10.1089/scd.2024.0178","url":null,"abstract":"<p><p>Autologous hematopoietic stem cell transplantation is used to restore bone marrow function after high-dose chemotherapy. For apheresis, granulocyte colony-stimulating factor (G-CSF) is standard of care, but obtaining sufficient stem cells can be challenging. Other mobilization agents include plerixafor and PEGylated G-CSF (PEG-G-CSF). While efficacy of these is established in adults, limited data for their use in pediatric patients are available. Here, we compare Good versus Poor Mobilizers and study success of different mobilization regimens in regard to CD34⁺cell-collection, -quality, -phenotype and hematologic reconstitution in pediatric patients. In this multi-center retrospective study, we analyzed data of 278 patients with solid tumors and lymphoma, mobilized with either G-CSF (<i>n</i> = 224), PEG-G-CSF (<i>n</i> = 34), or G-CSF/PEG-G-CSF with additional plerixafor (<i>n</i> = 20). In Poor Mobilizers (13.7% of all patients), addition of plerixafor to G-CSF augmented CD34⁺cell collection, without adverse effects on hematologic reconstitution and CD34⁺cell quality. PEG-G-CSF-aided mobilization was successful as first-line treatment in two-thirds of patients and did not impair hematological reconstitution, compared to G-CSF-only. Within the Poor Mobilizer group, G-CSF+plerixafor increased primitive (CD45RA^-CD38^-CD90⁺CD49f⁺) and CXCR4-expressing CD34⁺cells in apheresis products compared to G-CSF-only, without exceeding levels of Good Mobilizers. No plerixafor-related increase in tumor cells was observed in apheresis products. In conclusion, our comprehensive study supports the use of plerixafor and furthermore demonstrates the potential of patient-friendly PEG-G-CSF for mobilization of pediatric patients.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"61-72"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019319","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":"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":"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":"49-60"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","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}

{"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":"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^-CD45^- and LIN^-CD45⁺ 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":"35-47"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","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}

{"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}