Stem Cells Translational Medicine最新文献

{"title":"eIF6 modulates skin wound healing by upregulating keratin 6B.","authors":"Xiaoyan Wang, Guangchao Xu, Fangyingnan Zhang, Yating Wei, Jiawen Deng, Lan Mu, Jinqing He, Dehua He, Meifang Yin, Ilaria Dal Pra, Xiaofang Liu, Weichao Cai, Linjing Yang, Chunmao Han, Guangtao Huang, Jun Wu","doi":"10.1093/stcltm/szae064","DOIUrl":"10.1093/stcltm/szae064","url":null,"abstract":"<p><p>Eukaryotic translation initiation factor 6 (eIF6) plays a crucial role in 60S ribosome biogenesis and protein translation, as well as in hypertrophic scar formation, but its potential role in epithelialization is still poorly understood. Herein, we found that eIF6 negatively correlated with the wound healing process. Mice with genetically knockdown eIF6 (eIF6+/-) showed faster re-epithelization as shown by the longer tongue of the newly formed epidermis. Furthermore, eIF6 ablation accelerated the wound healing process by targeting basal keratinocytes in the eIF6 keratinocyte-conditional knockout (eIF6f/+; Krt5-Cre+) mice. Mechanistically, keratin 6B, an important wound-activated protein, was significantly upregulated in eIF6f/+; Krt5-Cre+ mice skin as proved by RNA-seq, western immunoblots, and immunofluorescence staining. Moreover, an elevated level of KRT6B and accelerated proliferative capacity were also observed in stable knockdown eIF6 HaCaT cells. Taken together, eIF6 downregulation could accelerate epithelialization by upregulating KRT6B expression and promoting keratinocyte proliferation. Our results for the first time indicate that eIF6 might be a novel target to regulate re-epithelialization.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1101-1112"},"PeriodicalIF":5.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent progress in modeling and treating diabetes using stem cell-derived islets.","authors":"Marlie M Maestas, Maggie H Bui, Jeffrey R Millman","doi":"10.1093/stcltm/szae059","DOIUrl":"10.1093/stcltm/szae059","url":null,"abstract":"<p><p>Stem cell-derived islets (SC-islets) offer the potential to be an unlimited source of cells for disease modeling and the treatment of diabetes. SC-islets can be genetically modified, treated with chemical compounds, or differentiated from patient derived stem cells to model diabetes. These models provide insights into disease pathogenesis and vulnerabilities that may be targeted to provide treatment. SC-islets themselves are also being investigated as a cell therapy for diabetes. However, the transplantation process is imperfect; side effects from immunosuppressant use have reduced SC-islet therapeutic potential. Alternative methods to this include encapsulation, use of immunomodulating molecules, and genetic modification of SC-islets. This review covers recent advances using SC-islets to understand different diabetes pathologies and as a cell therapy.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"949-958"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the future of clinical trials and translation of mesenchymal stromal cell therapies for neonatal disorders.","authors":"Yun Sil Chang, Misun Yang, So Yoon Ahn, Se In Sung, Won Soon Park","doi":"10.1093/stcltm/szae060","DOIUrl":"10.1093/stcltm/szae060","url":null,"abstract":"<p><p>Despite recent advances in neonatal intensive care medicine, neonatal disorders such as (bronchopulmonary dysplasia [BPD], intraventricular hemorrhage [IVH], and hypoxic ischemic encephalopathy [HIE]) remain major causes of death and morbidity in survivors, with few effective treatments being available. Recent preclinical studies have demonstrated the pleiotropic host injury-responsive paracrine protective effects of cell therapy especially with mesenchymal stromal cells (MSCs) against BPD, IVH, and HIE. These findings suggest that MSCs therapy might emerge as a novel therapeutic modality for these currently devastating neonatal disorders with complex multifactorial etiologies. Although early-phase clinical trials suggest their safety and feasibility, their clinical therapeutic benefits have not yet been proven. Therefore, based on currently available preclinical research and clinical trial data, we focus on critical issues that need to be addressed for future successful clinical trials and eventual clinical translation such as selecting the right patient and optimal cell type, route, dose, and timing of MSCs therapy for neonatal disorders such as BPD, HIE, and IVH.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"941-948"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of compression forces on different mesenchymal stem cell types regarding orthodontic indication.","authors":"Chloé Radermacher, Rogerio B Craveiro, Wilhelm Jahnen-Dechent, Justus P Beier, Astrid Bülow, Michael Wolf, Sabine Neuss","doi":"10.1093/stcltm/szae057","DOIUrl":"10.1093/stcltm/szae057","url":null,"abstract":"<p><p>The potential of stem cells, for example upper periodontal ligament stem cells from the maxilla (u-PDLSC) and from the mandible (l-PDLSC), adipose-derived mesenchymal stem cells (AD-MSC), and bone marrow-derived mesenchymal stem cells (BM-MSC), with respect to periodontal remodeling and orthodontic treatment is of great importance. In this work, we focus on the comprehensive adaptability of different stem cell types to mechanical forces with the aim to better understanding cell behavior and to refine a new mechanistic approach to investigate periodontal remodeling. We comprehensively analyze stem cells and observe distinct morphological and proliferation changes under compression in dependence on stem cell type. The cell signaling of extracellular signal-regulated kinase (ERK) and protein kinase B, also called AKT, and their respective phosphorylation shows diverse responses to compression. Additionally, vascular endothelial growth factor and hepatocyte growth factor secretion were reduced under mechanical stress in all cell types, with cell-specific variations. Osteoprotegerin secretion was reduced under compression, particularly in u-PDLSC. At least, diverse soluble receptors of NF-kB-ligand secretion patterns among cell types under pressure were observed, providing crucial insights into bone metabolism. These findings offer a deeper understanding of the behavior of mesenchymal stem cells under mechanical stimuli, highlighting their roles in bone remodeling, wound healing, and tissue regeneration in orthodontic and regenerative medicine contexts. Our results underscore the potential of u-PDLSC, l-PDLSC, and AD-MSC in periodontal regeneration, with AD-MSC showing notable resilience under compression, indicating its promising role for further investigation for orthodontic research. While these findings are encouraging, further research is essential to fully comprehend the mechanism of stem cell-based periodontal therapies.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1028-1039"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of residual pluripotent stem cells in cell therapy products utilizing droplet digital PCR: an international multisite evaluation study.","authors":"Satoshi Yasuda, Kiyoko Bando, Marianne P Henry, Silvana Libertini, Takeshi Watanabe, Hiroto Bando, Connie Chen, Koki Fujimori, Kosuke Harada, Takuya Kuroda, Myriam Lemmens, Dragos Marginean, David Moss, Lucilia Pereira Mouriès, Nicole S Nicholas, Matthew J K Smart, Orie Terai, Yoji Sato","doi":"10.1093/stcltm/szae058","DOIUrl":"10.1093/stcltm/szae058","url":null,"abstract":"<p><p>The presence of residual undifferentiated pluripotent stem cells (PSCs) in PSC-derived cell therapy products (CTPs) is a major safety issue for their clinical application, due to the potential risk of PSC-derived tumor formation. An international multidisciplinary multisite study to evaluate a droplet digital PCR (ddPCR) approach to detect residual undifferentiated PSCs in PSC-derived CTPs was conducted as part of the Health and Environmental Sciences Institute Cell Therapy-TRAcking, Circulation & Safety Technical Committee. To evaluate the use of ddPCR in quantifying residual iPSCs in a cell sample, different quantities of induced pluripotent stem cells (iPSCs) were spiked into a background of iPSC-derived cardiomyocytes (CMs) to mimic different concentrations of residual iPSCs. A one step reverse transcription ddPCR (RT-ddPCR) was performed to measure mRNA levels of several iPSC-specific markers and to evaluate the assay performance (precision, sensitivity, and specificity) between and within laboratories. The RT-ddPCR assay variability was initially assessed by measuring the same RNA samples across all participating facilities. Subsequently, each facility independently conducted the entire process, incorporating the spiking step, to discern the parameters influencing potential variability. Our results show that a RT-ddPCR assay targeting ESRG, LINC00678, and LIN28A genes offers a highly sensitive and robust detection of impurities of iPSC-derived CMs and that the main contribution to variability between laboratories is the iPSC-spiking procedure, and not the RT-ddPCR. The RT-ddPCR assay would be generally applicable for tumorigenicity evaluation of PSC-derived CTPs with appropriate marker genes suitable for each CTP.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1001-1014"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel long noncoding RNA AK029592 contributes to thermogenic adipocyte differentiation.","authors":"Pengyu Hong, Dianri Wang, Yue Wu, Qi Zhang, Pan Liu, Jian Pan, Mei Yu, Weidong Tian","doi":"10.1093/stcltm/szae056","DOIUrl":"10.1093/stcltm/szae056","url":null,"abstract":"<p><p>Exploration of factors originating from brown adipose tissue that govern the thermogenic adipocyte differentiation is imperative for comprehending the regulatory framework underlying brown fat biogenesis and for devising therapeutic approaches for metabolic disorders associated with obesity. Prior evidence has illuminated the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating thermogenesis within adipose tissue. Here, we aimed to explore and identify the critical lncRNA that could promote thermogenic adipocyte differentiation and to provide a novel strategy to treat obesity-related metabolic diseases in the future. In this study, through amalgamation with our previous lncRNA microarray data from small extracellular vesicles derived from BAT (sEV-BAT), we have identified sEV-BAT-enriched lncRNA AK029592 as a critical constituent of the thermogenic program, which actively fostered beige adipocyte differentiation and enhanced the thermogenic capacities of adipose tissue. Moreover, lncRNA AK029592 could sponge miR-199a-5p in adipocytes to stimulate thermogenic gene expression. Consequently, we concluded lncRNA AK029592 as a crucial lncRNA component of the thermogenic program that regulated beige adipocyte differentiation and white adipose tissue browning, thereby providing a novel therapeutic target and strategy in combating obesity and related metabolic diseases.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"985-1000"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryopreserved apoptotic mesenchymal stromal cells retain functional efficacy in suppressing an allergic inflammation in a murine model.","authors":"Richard T Amison, Tik S Cheung, Chiara Giacomini, Yanira Riffo-Vasquez, Antonio Galleu, Roberto Savoldelli, Ryan Hicks, Anna Kozlowska, Francesco Dazzi","doi":"10.1093/stcltm/szae061","DOIUrl":"10.1093/stcltm/szae061","url":null,"abstract":"<p><p>Mesenchymal stromal cell (MSC) apoptosis is required for in vivo immunosuppression. However, the induction of apoptosis is heavily dependent on the recipient's immune system. In graft-versus-host disease (GvHD), patients who fail to respond to MSCs are in fact those whose immune cells are unable to induce MSC apoptosis ex vivo. The information is critical to explain why responses in clinical trials vary even though the same sources of MSC products are infused. More importantly, it highlights the need for an alternative MSC treatment for the nonresponders. By using a mouse model of ovalbumin (OVA)-induced allergic inflammation, we demonstrated that we could generate apoptotic MSCs (ApoMSCs) in vitro and use them to successfully reduce allergic airway inflammation. In order to address the logistics of their potential future clinical application, we have shown that ApoMSCs could be cryopreserved without impairing efficacy compared to freshly generated ApoMSCs. We have also highlighted that MSCs need to undergo complete apoptosis before cryopreservation to retain their immunosuppressive activity. The cryopreserved ApoMSCs could serve as a potential future off-the-shelf cellular product, in particular for patients who suffer from inflammatory conditions yet do not harbor the immune capacity to induce MSC apoptosis in vivo. Our data provide proof-of-concept that under laboratory conditions, ApoMSCs can be successfully frozen and thawed without affecting their anti-inflammatory activity, as tested in a murine model of allergic inflammation.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"979-984"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: NLRP3 and AIM2 inflammasomes expression is modified by LPS and titanium ions increasing the release of active IL-1β in alveolar bone-derived MSCs.","authors":"","doi":"10.1093/stcltm/szae068","DOIUrl":"10.1093/stcltm/szae068","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1040-1042"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-based therapy in the treatment of musculoskeletal diseases.","authors":"Justin Trapana, Jonathan Weinerman, Danny Lee, Anil Sedani, David Constantinescu, Thomas M Best, Francis J Hornicek, Joshua M Hare","doi":"10.1093/stcltm/szae049","DOIUrl":"10.1093/stcltm/szae049","url":null,"abstract":"<p><p>A limited number of tissues can spontaneously regenerate following injury, and even fewer can regenerate to a state comparable to mature, healthy adult tissue. Mesenchymal stem cells (MSCs) were first described in the 1960s-1970s by Friedenstein et al as a small population of bone marrow cells with osteogenic potential and abilities to differentiate into chondrocytes. In 1991, Arnold Caplan coined the term \"mesenchymal cells\" after identifying these cells as a theoretical precursor to bone, cartilage, tendon, ligament, marrow stroma, adipocyte, dermis, muscle, and connective tissues. MSCs are derived from periosteum, fat, and muscle. Another attractive property of MSCs is their immunoregulatory and regenerative properties, which result from crosstalk with their microenvironment and components of the innate immune system. Collectively, these properties make MSCs potentially attractive for various therapeutic purposes. MSCs offer potential in sports medicine, aiding in muscle recovery, meniscal tears, and tendon and ligament injuries. In joint disease, MSCs have the potential for chondrogenesis and reversing the effects of osteoarthritis. MSCs have also demonstrated potential application to the treatment of degenerative disc disease of the cervical, thoracic, and lumbar spine.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"959-978"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A detailed survey of the murine limbus, its stem cell distribution, and its boundaries with the cornea and conjunctiva.","authors":"Lamia Nureen, Joanna Biazik, Michael Carnell, Nick Di Girolamo","doi":"10.1093/stcltm/szae055","DOIUrl":"10.1093/stcltm/szae055","url":null,"abstract":"<p><p>The narrow intersection between the cornea and conjunctiva, otherwise known as the limbus, is purported to harbor stem cells (SCs) that replenish the ocular surface epithelium throughout life. Damage to this site or depletion of its SCs can have dire consequences for eye health and vision. To date, various SC and keratin proteins have been used to identify the limbus, however, none could definitively mark its boundaries. Herein, we use the mouse as a model system to investigate whether structural and phenotypic features can be used to define the limbus and its boundaries with adjacent tissues. We demonstrate that differentially aligned blood and lymphatic vessels, intraepithelial nerves, and basal epithelial cellular and nuclei dimensions can be used as structural landmarks of the limbus. Identification of these features enabled approximation of the limbal expanse, which varied across distinct ocular surface quadrants, with the superior nasal and inferior temporal limbus being the widest and narrowest, respectively. Moreover, label-retaining SCs were unevenly distributed across the ocular circumference, with increased numbers in the superior temporal and inferior temporal moieties. These findings will heighten our current understanding of the SC niche, be beneficial for accurately predicting SC distribution to improve their isolation and devising efficacious cell therapies, and importantly, aid the ongoing search for novel SC markers.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1015-1027"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}