Stem Cells Translational Medicine最新文献

{"title":"Agrin Inhibition in Enteric Neural Stem Cells Enhances Their Migration Following Colonic Transplantation.","authors":"Jessica L Mueller, Rhian Stavely, Richard A Guyer, Ádám Soos, Sukhada Bhave, Chris Han, Ryo Hotta, Nandor Nagy, Allan M Goldstein","doi":"10.1093/stcltm/szae013","DOIUrl":"10.1093/stcltm/szae013","url":null,"abstract":"<p><p>Regenerative cell therapy to replenish the missing neurons and glia in the aganglionic segment of Hirschsprung disease represents a promising treatment option. However, the success of cell therapies for this condition are hindered by poor migration of the transplanted cells. This limitation is in part due to a markedly less permissive extracellular environment in the postnatal gut than that of the embryo. Coordinated interactions between enteric neural crest-derived cells (ENCDCs) and their local environment drive migration along the embryonic gut during development of the enteric nervous system. Modifying transplanted cells, or the postnatal extracellular environment, to better recapitulate embryonic ENCDC migration could be leveraged to improve the engraftment and coverage of stem cell transplants. We compared the transcriptomes of ENCDCs from the embryonic intestine to that of postnatal-derived neurospheres and identified 89 extracellular matrix (ECM)-associated genes that are differentially expressed. Agrin, a heparin sulfate proteoglycan with a known inhibitory effect on ENCDC migration, was highly over-expressed by postnatal-derived neurospheres. Using a function-blocking antibody and a shRNA-expressing lentivirus, we show that inhibiting agrin promotes ENCDC migration in vitro and following cell transplantation ex vivo and in vivo. This enhanced migration is associated with an increased proportion of GFAP + cells, whose migration is especially enhanced.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"490-504"},"PeriodicalIF":5.4,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932965","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":"The Treatment of Refractory Vitiligo With Autologous Cultured Epithelium Grafting: A Real-World Retrospective Cohort Study.","authors":"Jian Li, Xuanhao Zeng, Shujun Chen, Luyan Tang, Qi Zhang, Minzi Lv, Weiling Lian, Jinqi Wang, Haozhen Lv, Yating Liu, Jiayi Shen, Taro Uyama, Fuyue Wu, Jinfeng Wu, Jinhua Xu","doi":"10.1093/stcltm/szae009","DOIUrl":"10.1093/stcltm/szae009","url":null,"abstract":"<p><strong>Background: </strong>Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented. Using a generalized linear mixed model, we were able to assess the association between these characteristics and the repigmentation rate.</p><p><strong>Results: </strong>ACEG demonstrated a total efficacy rate of 82.81% (1754/2118) in treating 726 patients, with a higher repigmentation rate of 64.87% compared to conventional surgery at 52.69%. Notably, ACEG showed a better response in treating segmental vitiligo, lesions on lower limbs, age ≤ 18, and stable period > 3 years. A keratinocyte:melanocyte ratio below 25 was found to be advantageous too. Single-cell RNA sequencing analysis revealed an increase in melanocyte count and 2 subclusters of keratinocytes after ACEG, which remained higher in repigmented sites even after 1 year.</p><p><strong>Conclusions: </strong>ACEG is a promising therapy for refractory vitiligo. Patient age, clinical type, lesion site, and stability before surgery influence repigmentation in ACEG. The mechanism of repigmentation after ACEG treatment is likely not confined to the restoration of melanocyte populations. It may also involve an increase in the number of keratinocytes that support melanocyte function within the affected area. These keratinocytes may aid the post-transplant survival and function of melanocytes by secreting cytokines and extracellular matrix components.</p><p><strong>Trial registration: </strong>registered with Chictr.org.cn (ChiCTR2100051405).</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"415-424"},"PeriodicalIF":6.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185641","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":"Conditioned Medium From Stem Cells of Human Exfoliated Deciduous Teeth Alleviates Mouse Osteoarthritis by Inducing sFRP1-Expressing M2 Macrophages.","authors":"Linze Xia, Fumiya Kano, Noboru Hashimoto, Yao Liu, Tsendsuren Khurel-Ochir, Naoko Ogasawara, Cheng Ding, Yang Xu, Hideharu Hibi, Tomonori Iwasaki, Eiji Tanaka, Akihito Yamamoto","doi":"10.1093/stcltm/szae006","DOIUrl":"10.1093/stcltm/szae006","url":null,"abstract":"<p><p>Intravenous administration of conditioned medium from stem cells of human exfoliated deciduous teeth (SHED-CM) regenerates mechanically injured osteochondral tissues in mouse temporomandibular joint osteoarthritis (TMJOA). However, the underlying therapeutic mechanisms remain unclear. Here, we showed that SHED-CM alleviated injured TMJ by inducing anti-inflammatory M2 macrophages in the synovium. Depletion of M2 by Mannosylated Clodrosome abolished the osteochondral repair activities of SHED-CM. Administration of CM from M2-induced by SHED-CM (M2-CM) effectively ameliorated mouse TMJOA by inhibiting chondrocyte inflammation and matrix degradation while enhancing chondrocyte proliferation and matrix formation. Notably, in vitro, M2-CM directly suppressed the catabolic activities while enhancing the anabolic activities of interleukin-1β-stimulated mouse primary chondrocytes. M2-CM also inhibited receptor activator of nuclear factor NF-κB ligand-induced osteoclastogenesis in RAW264.7 cells. Secretome analysis of M2-CM and M0-CM revealed that 5 proteins related to anti-inflammation and/or osteochondrogenesis were enriched in M2-CM. Of these proteins, the Wnt signal antagonist, secreted frizzled-related protein 1 (sFRP1), was the most abundant and played an essential role in the shift to anabolic chondrocytes, suggesting that M2 ameliorated TMJOA partly through sFRP1. This study suggests that secretome from SHED exerted remarkable osteochondral regeneration activities in TMJOA through the induction of sFRP1-expressing tissue-repair M2 macrophages.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"399-413"},"PeriodicalIF":6.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747409","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":"Mesenchymal Stem Cells-Derived Exosomes Alleviate Acute Lung Injury by Inhibiting Alveolar Macrophage Pyroptosis.","authors":"Peipei Liu, Shengnan Yang, Xuecheng Shao, Chen Li, Zai Wang, Huaping Dai, Chen Wang","doi":"10.1093/stcltm/szad094","DOIUrl":"10.1093/stcltm/szad094","url":null,"abstract":"<p><p>Acute lung injury (ALI) is an important pathological process of acute respiratory distress syndrome, yet there are limited therapies for its treatment. Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been shown to be effective in suppressing inflammation. However, the effects of MSCs-Exo on ALI and the underlying mechanisms have not been well elucidated. Our data showed that MSCs-Exo, but not exosomes derived from MRC-5 cells (MRC-5-Exo), which are human fetal lung fibroblast cells, significantly improved chest imaging, histological observations, alveolocapillary membrane permeability, and reduced inflammatory response in ALI mice model. According to miRNA sequencing and proteomic analysis of MSCs-Exo and MRC-5-Exo, MSCs-Exo may inhibit pyroptosis by miRNAs targeting caspase-1-mediated pathway, and by proteins with immunoregulation functions. Taken together, our study demonstrated that MSCs-Exo were effective in treating ALI by inhibiting the pyroptosis of alveolar macrophages and reducing inflammation response. Its mechanism may be through pyroptosis-targeting miRNAs and immunoregulating proteins delivered by MSCs-Exo. Therefore, MSCs-Exo may be a new treatment option in the early stage of ALI.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"371-386"},"PeriodicalIF":6.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724024","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":"Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cell Therapy in Preclinical Models of Sepsis: A Systematic Review and Meta-analysis.","authors":"Christine Hum, Usama Tahir, Shirley H J Mei, Josee Champagne, Dean A Fergusson, Manoj Lalu, Duncan J Stewart, Keith Walley, John Marshall, Claudia C Dos Santos, Brent W Winston, Asher A Mendelson, Chintan Dave, Lauralyn McIntyre","doi":"10.1093/stcltm/szae003","DOIUrl":"10.1093/stcltm/szae003","url":null,"abstract":"<p><strong>Background: </strong>In preclinical studies, mesenchymal stromal cells (MSCs), including umbilical cord-derived MSCs (UC-MSCs), demonstrate the ability to modulate numerous pathophysiological processes related to sepsis; however, a systematic synthesis of the literature is needed to assess the efficacy of UC-MSCs for treating sepsis.</p><p><strong>Objective: </strong>To examine the effects of UC-MSCs on overall mortality (primary outcome) as well as on organ dysfunction, coagulopathy, endothelial permeability, pathogen clearance, and systemic inflammation (secondary outcomes) at prespecified time intervals in preclinical models of sepsis.</p><p><strong>Methods: </strong>A systematic search was conducted on Embase, Ovid MEDLINE, and Web of Science up to June 20, 2023. Preclinical controlled studies using in vivo sepsis models with systemic UC-MSC administration were included. Meta-analyses were conducted and expressed as odds ratios (OR) and ratios of the weighted means with 95% CI for categorical and continuous data, respectively. Risk of bias was assessed with the SYRCLE tool.</p><p><strong>Results: </strong>Twenty-six studies (34 experiments, n = 1258 animals) were included in this review. Overall mortality was significantly reduced with UC-MSC treatment as compared to controls (OR: 0.26, 95% CI: 0.18-0.36). At various prespecified time intervals, UC-MSCs reduced surrogate measures of organ dysfunction related to the kidney, liver, and lung; reduced coagulopathy and endothelial permeability; and enhanced pathogen clearance from multiple sites. UC-MSCs also modulated systemic inflammatory mediators. No studies were rated as low risk across all SYCLE domains.</p><p><strong>Conclusions: </strong>These results demonstrate the efficacy of UC-MSC treatment in preclinical sepsis models and highlight their potential as a therapeutic intervention for septic shock.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"346-361"},"PeriodicalIF":5.4,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932967","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 Photoreceptor Cell-Based Therapy for Degenerative Retinal Disease.","authors":"Valeriia Klymenko, Orlando G González Martínez, Marco A Zarbin","doi":"10.1093/stcltm/szae005","DOIUrl":"10.1093/stcltm/szae005","url":null,"abstract":"<p><p>Age-related macular degeneration and retinitis pigmentosa are degenerative retinal diseases that cause severe vision loss. Early clinical trials involving transplantation of photoreceptors as treatment for these conditions are underway. In this review, we summarize recent progress in the field of photoreceptor transplantation, including some pertinent results regarding photoreceptor manufacture, photoreceptor transplantation, mechanisms of donor-host cell integration such as material transfer and photoreceptor transplant immunology. We conclude by proposing several approaches that may provide a rational basis for selecting a vision restoration strategy (eg, donor-host synapse formation vs donor-host nanotube formation) and improved transplant efficiency.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"332-345"},"PeriodicalIF":6.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991200","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 Retinal Pigment Epithelium Cell-Based Therapy for Retinal Disease.","authors":"Valeriia Klymenko, Orlando G González Martínez, Marco Zarbin","doi":"10.1093/stcltm/szae004","DOIUrl":"10.1093/stcltm/szae004","url":null,"abstract":"<p><p>Age-related macular degeneration and retinitis pigmentosa are degenerative retinal diseases that cause severe vision loss. Early clinical trials involving transplantation of retinal pigment epithelial cells and/or photoreceptors as a treatment for these conditions are underway. In this review, we summarize recent progress in the field of retinal pigment epithelium transplantation, including some pertinent clinical trial results as well as preclinical studies that address issues of transplant immunology, cell delivery, and cell manufacturing.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"317-331"},"PeriodicalIF":6.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940812","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":"Label-Free and High-Throughput Removal of Residual Undifferentiated Cells From iPSC-Derived Spinal Cord Progenitor Cells.","authors":"Tan Dai Nguyen, Wai Hon Chooi, Hyungkook Jeon, Jiahui Chen, Jerome Tan, Daniel N Roxby, Cheryl Yi-Pin Lee, Shi-Yan Ng, Sing Yian Chew, Jongyoon Han","doi":"10.1093/stcltm/szae002","DOIUrl":"10.1093/stcltm/szae002","url":null,"abstract":"<p><p>The transplantation of spinal cord progenitor cells (SCPCs) derived from human-induced pluripotent stem cells (iPSCs) has beneficial effects in treating spinal cord injury (SCI). However, the presence of residual undifferentiated iPSCs among their differentiated progeny poses a high risk as these cells can develop teratomas or other types of tumors post-transplantation. Despite the need to remove these residual undifferentiated iPSCs, no specific surface markers can identify them for subsequent removal. By profiling the size of SCPCs after a 10-day differentiation process, we found that the large-sized group contains significantly more cells expressing pluripotent markers. In this study, we used a sized-based, label-free separation using an inertial microfluidic-based device to remove tumor-risk cells. The device can reduce the number of undifferentiated cells from an SCPC population with high throughput (ie, >3 million cells/minute) without affecting cell viability and functions. The sorted cells were verified with immunofluorescence staining, flow cytometry analysis, and colony culture assay. We demonstrated the capabilities of our technology to reduce the percentage of OCT4-positive cells. Our technology has great potential for the \"downstream processing\" of cell manufacturing workflow, ensuring better quality and safety of transplanted cells.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"387-398"},"PeriodicalIF":6.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699248","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":"Optimal Therapeutic Strategy of Bone Marrow-Originated Autologous Mesenchymal Stromal/Stem Cells for ALS.","authors":"Seung Hyun Kim, Ki-Wook Oh, Min-Young Noh, Min-Soo Kwon","doi":"10.1093/stcltm/szad095","DOIUrl":"10.1093/stcltm/szad095","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is characterized by selective and progressive neurodegenerative changes in motor neural networks. Given the system complexity, including anatomically distributed sites of degeneration from the motor cortex to the spinal cord and chronic pro-inflammatory conditions, a cell-based therapeutic strategy could be an alternative approach to treating ALS. Lessons from previous mesenchymal stromal/stem cell (MSC) trials in ALS realized the importance of 3 aspects in current and future MSC therapy, including the preparation of MSCs, administration routes and methods, and recipient-related factors. This review briefly describes the current status and future prerequisites for an optimal strategy using bone-marrow-originated MSCs to treat ALS. We suggest mandatory factors in the optimized therapeutic strategy focused on advanced therapy medicinal products produced according to Good Manufacturing Practice, an optimal administration method, the selection of proper patients, and the importance of biomarkers.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"309-316"},"PeriodicalIF":6.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513661","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":"Direct Reprogramming of Fibroblasts to Osteoblasts: Techniques and Methodologies.","authors":"Asghar Fallah, Alexander Beke, Connor Oborn, Carrie-Lynn Soltys, Peter Kannu","doi":"10.1093/stcltm/szad093","DOIUrl":"10.1093/stcltm/szad093","url":null,"abstract":"<p><p>Direct reprogramming (DR) is an emerging technique that can be applied to convert fibroblasts into osteoblast-like cells, promoting bone formation and regeneration. We review the current methodology of DR in relation to the creation of induced osteoblasts, including a comparison of transcription factor-mediated reprogramming and nontranscription factor-mediated reprogramming. We review the selection of reprogramming factors and delivery systems required. Transcription factor cocktails, such as the RXOL cocktail (Runx2, Osx, OCT3/4, and L-MYC), have shown promise in inducing osteogenic differentiation in fibroblasts. Alterations to the original cocktail, such as the addition of Oct9 and N-myc, have resulted in improved reprogramming efficiency. Transcription factor delivery includes integrative and nonintegrative systems which encompass viral vectors and nonviral methods such as synthetic RNA. Recently, an integrative approach using self-replicating RNA has been developed to achieve a longer and more sustained transcription factor expression. Nontranscription factor-mediated reprogramming using small molecules, proteins, inhibitors, and agonists has also been explored. For example, IGFBP7 protein supplementation and ALK5i-II inhibitor treatment have shown potential in enhancing osteoblast reprogramming. Direct reprogramming methods hold great promise for advancing bone regeneration and tissue repair, providing a potential therapeutic approach for fracture healing and the repair of bone defects. Multiple obstacles and constraints need to be addressed before a clinically significant level of cell therapy will be reached. Further research is needed to optimize the efficiency of the reprogramming cocktails, delivery methods, and safety profile of the reprogramming process.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"362-370"},"PeriodicalIF":6.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074987","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}