Regenerative Therapy最新文献

{"title":"Alpha terpineol preconditioning enhances regenerative potential of mesenchymal stem cells in full thickness acid burn wounds","authors":"Fatima Jameel ,&nbsp;Fatima Irfan ,&nbsp;Asmat Salim ,&nbsp;Irfan Khan ,&nbsp;Enam A. Khalil","doi":"10.1016/j.reth.2024.05.008","DOIUrl":"https://doi.org/10.1016/j.reth.2024.05.008","url":null,"abstract":"<div><p>Regeneration of full thickness burn wounds is a significant clinical challenge. Direct stem cell transplantation at the wound site has a promising effect on wound regeneration. However, stem cell survival within the harsh wound environment is critically compromised. In this regard, preconditioning of stem cells with cytoprotective compounds can improve the efficiency of transplanted cells. This study evaluated the possible effect of alpha terpineol (αT) preconditioned mesenchymal stem cells (αT-MSCs) in full thickness acid burn wound. An optimized concentration of 10 μM αT was used for MSC preconditioning, followed by scratch assay analysis. A novel rat model of full thickness acid burn wound was developed and characterized <em>via</em> macroscopic and histological examinations. Treatment (normal and αT-MSCs) was given after 48 h of burn wound induction, and the healing pattern was examined till day 40. Skin tissues were harvested at the early (day 10) and late (day 40) wound healing phases and examined by histological grading, neovascularization, and gene expression profiling of healing mediators. In scratch assay, αT-MSCs exhibited enhanced cell migration and wound closure (scratch gap) compared to normal MSCs. <em>In vivo</em> findings revealed enhanced regeneration in the wound treated with αT-MSCs compared to normal MSCs and untreated control. Histology revealed enhanced collagen deposition with regenerated skin layers in normal MSC- and αT-MSC treated groups compared to the untreated control. These findings were correlated with enhanced expression of α-SMA as shown by immunohistochemistry. Additionally, αT-MSC group showed reduced inflammation and oxidative stress, and enhanced regeneration, as witnessed by a decrease in <em>IL-1β</em>, <em>IL-6</em>, <em>TNF-α</em>, and <em>Bax</em> and an increase in <em>BCL-2, PRDX-4, GPX-7,</em> <em>SOD-1</em>, <em>VEGF</em>, <em>EGF</em>, <em>FGF</em>, <em>MMP-9</em>, <em>PDGF</em>, and <em>TGF-β</em> gene expression levels at early and late phases, respectively. Overall findings demonstrated that αT exerts its therapeutic effect by mitigating excessive inflammation and oxidative stress while concurrently enhancing neovascularization. Thus, this study offers new perspectives on managing full thickness acid burn wounds in future clinical settings.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 188-202"},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000956/pdfft?md5=b689e7ebb23a24d7448357554326db58&pid=1-s2.0-S2352320424000956-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141294847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicle mimetics engineered from mesenchymal stem cells and curcumin promote fibrosis regression in a mouse model of thioacetamide-induced liver fibrosis","authors":"Arunnehru Gopal ,&nbsp;Prakash Gangadaran ,&nbsp;Ramya Lakshmi Rajendran ,&nbsp;Ji Min Oh ,&nbsp;Ho Won Lee ,&nbsp;Chae Moon Hong ,&nbsp;Senthilkumar Kalimuthu ,&nbsp;Man-Hoon Han ,&nbsp;Jaetae Lee ,&nbsp;Byeong-Cheol Ahn","doi":"10.1016/j.reth.2024.10.005","DOIUrl":"10.1016/j.reth.2024.10.005","url":null,"abstract":"<div><div>Recent research suggests that advanced liver fibrosis could be reversed, but the therapeutic agents needed for the prevention of liver fibrosis remain to be elucidated. The beneficial effects of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) on liver fibrosis have been reported. However, the large-scale production of MSC-EVs remains challenging. The present study investigated the therapeutic effects of mouse MSC-derived EV mimetics (MEVMs) in combination with curcumin (antifibrotic compound) using a mouse model of thioacetamide-induced liver fibrosis. MEVMs were prepared through the serial extrusion of MSCs. These MEVMs were similar in size and morphology to the EVs. The biodistribution study showed that fluorescently labeled MEVMs predominantly accumulated in the liver. The establishment of liver fibrosis was confirmed via increased collagen (histology), liver fibrosis score, α-smooth muscle actin (α-SMA), and vimentin proteins levels. Treatment with MEVMs, curcumin, or their combination decreased the amount of collagen in liver tissues, with the antifibrotic effects of MEVMs being further confirmed by the liver fibrosis score. All treatments decreased the expression of <em>collagen 1α</em>, α-SMA, and vimentin. MEVMs showed superior effects than curcumin. Thus, MSC-derived EVMs could be a potential alternative for the treatment of liver fibrosis.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 911-921"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial heterogeneity analysis of seeding of human induced pluripotent stem cells for neuroectodermal differentiation","authors":"Ali Ahmed Issa Qatan ,&nbsp;Shinji Tanbara ,&nbsp;Masakazu Inamori ,&nbsp;Kazuhiro Fukumori ,&nbsp;Masahiro Kino–oka","doi":"10.1016/j.reth.2024.10.006","DOIUrl":"10.1016/j.reth.2024.10.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Preparing a uniform cell population in high–density seeding of adherent human induced pluripotent stem cells (hiPSC) requires stable culture conditions and consistent culture operation. In this study, we evaluated cell distribution patterns by changing cell seeding operations and their impact on differentiation toward the neuroectodermal lineage.</div></div><div><h3>Methods</h3><div>The hiPSC line 201B7 was seeded at 1.23 × 10⁵ cells/cm² following a conventional operation, prolongated time of cell seeding suspension or vessel tilting during cell seeding operation. Fluorescent imaging of cell nuclei was performed 24 h following cell seeding and used for spatial heterogeneity analysis. Flow cytometric analysis was also performed seven days after cell differentiation induction toward neuroectodermal lineage.</div></div><div><h3>Results</h3><div>Indices for spatial heterogeneity following high–density cell seeding were proposed to assess cell distribution patterns. Global heterogeneity (<em>H</em>_G) was shown to be mostly affected by vessel tilting during cell seeding operation, while local heterogeneity (<em>H</em>_L) was affected by prolongated time of cell seeding suspension. Changes in both spatial heterogeneities in the hiPSC population resulted in a lower yield of target neuroectodermal cells compared with the control operation.</div></div><div><h3>Conclusion</h3><div>High–density hiPSC seeding is critical for achieving a higher yield of target cells of neuroectodermal lineage. Understanding the spatial heterogeneity in early stages detects errors in cell culture motion and predicts cell fate in later stages of cell culture.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 922-931"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of histone methyltransferase KMT2D in BMSC osteogenesis via AKT signaling","authors":"Zhichun Zhang ,&nbsp;Yanyan Guo ,&nbsp;Xuejun Gao ,&nbsp;Xiaoyan Wang ,&nbsp;Chanyuan Jin","doi":"10.1016/j.reth.2024.08.022","DOIUrl":"10.1016/j.reth.2024.08.022","url":null,"abstract":"<div><p>Understanding the precise mechanism of BMSC (bone marrow mesenchymal stem cell) osteogenesis is critical for metabolic bone diseases and bone reconstruction. The histone-lysine N-methyltransferase 2D (KMT2D) acts as an important methyltransferase related with congenital skeletal disorders, yet the function of KMT2D in osteogenesis was unclear. Here we found that KMT2D expression was decreased in BMSCs collected from ovariectomized mice. Moreover, during human BMSC differentiation under mineralization induction, the mRNA level of KMT2D was gradually elevated. After KMT2D knockdown, the <em>in vitro</em> osteogenic differentiation of BMSCs was inhibited, while the <em>in vivo</em> bone formation potential of BMSCs was attenuated. Further, in BMSCs, KMT2D knockdown reduced the level of phosphorylated protein kinase B (p-AKT). SC-79, a common activator of AKT signaling, reversed the suppressing influence of KMT2D knockdown on BMSCs differentiation towards osteoblast. These results indicate that the KMT2D-AKT pathway plays an essential role in the osteogenesis process of human BMSCs (hBMSCs), which might provide new avenues for the molecular medicine of bone diseases and regeneration.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 775-782"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001603/pdfft?md5=3d69e3697459454fafa0dbc0e0d4c435&pid=1-s2.0-S2352320424001603-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful transport across continents of GMP-manufactured and cryopreserved culture-expanded human fetal liver-derived mesenchymal stem cells for use in a clinical trial","authors":"Ashis Kumar ,&nbsp;Sowmya Ramesh ,&nbsp;Lilian Walther-Jallow ,&nbsp;Annika Goos ,&nbsp;Vignesh Kumar ,&nbsp;Åsa Ekblad ,&nbsp;Vrisha Madhuri ,&nbsp;Cecilia Götherström","doi":"10.1016/j.reth.2024.06.012","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.012","url":null,"abstract":"<div><h3>Introduction</h3><p>Cell therapy has been increasingly considered to treat diseases, but it has been proven difficult to manufacture the same product at multiple manufacturing sites. Thus, for a wider implementation an alternative is to have one manufacturing site with a wide distribution to clinical sites. To ensure administration of a good quality cell therapy product with maintained functional characteristics, several obstacles must be overcome, which includes for example transfer of knowledge, protocols and procedures, site assessment, transportation and preparation of the product.</p></div><div><h3>Methods</h3><p>As the preparatory work for a clinical trial in India using fetal mesenchymal stem cells (fMSCs) developed and manufactured in Sweden, we performed a site assessment of the receiving clinical site, transferred methods, developed procedures and provided training of operators for handling of the cell therapy product. We further developed a Pharmacy Manual to cover the management of the product, from ordering it from the manufacturer, through transport, reconstitution, testing and administration at the clinical site. Lastly, the effect of long-distance transport on survival and function of, as well as the correct handling of the cell therapy product, was evaluated according to the pre-determined and approved Product Specification.</p></div><div><h3>Results</h3><p>Four batches of cryopreserved human fetal liver-derived fMSCs manufactured according to Good Manufacturing Practice and tested according to predetermined release criteria in Sweden, were certified and transported in a dry shipper at −150 °C to the clinical site in India. The transport was temperature monitored and took three–seven days to complete. The thawed and reconstituted cells showed more than 80% viability up to 3 h post-thawing, the cell recovery was more than 94%, the cells displayed the same surface protein expression pattern, differentiated into bone, had stable chromosomes and were sterile, which conformed with the data from the manufacturing site in Sweden.</p></div><div><h3>Conclusions</h3><p>Our study shows the feasibility of transferring necessary knowledge and technology to be able to carry out a clinical trial with a cell therapy product in distant country. It also shows that it is possible to transport a cryopreserved cell therapy product over long distances and borders with retained quality. This extends the use of cryopreserved cell therapy products in the future.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 324-333"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001196/pdfft?md5=e4c1c790ee29540bc9cc1b1671706fc3&pid=1-s2.0-S2352320424001196-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141483233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cartilage responses to inflammatory stimuli and adipose stem/stromal cell-derived conditioned medium: Results from an ex vivo model","authors":"Francesca Cadelano ,&nbsp;Elena Della Morte ,&nbsp;Stefania Niada ,&nbsp;Francesco Anzano ,&nbsp;Luigi Zagra ,&nbsp;Chiara Giannasi ,&nbsp;Anna Teresa Maria Brini","doi":"10.1016/j.reth.2024.06.010","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.010","url":null,"abstract":"<div><h3>Introduction</h3><p>Osteoarthritis (OA), a chronic inflammatory joint disorder, still lacks effective therapeutic interventions. Consequently, the development of convenient experimental models is crucial. Recently, research has focused on the plasticity of Mesenchymal Stem/stromal Cells, particularly adipose-derived ones (ASCs), in halting OA progression. This study investigates the therapeutic potential of a cell-free approach, ASC-derived conditioned medium (CM), in reversing cytokine-induced OA markers in an <em>ex vivo</em> model of human cartilage explants.</p></div><div><h3>Methods</h3><p>4 mm cartilage punches, derived from the femoral heads of patients undergoing total hip replacement, were treated with 10 ng/ml TNFα, 1 ng/ml IL-1β, or a combination of both, over a 3-day period. Analysis of OA-related markers, such as MMP activity, the release of NO and GAGs, and the expression of <em>PTGS2</em>, allowed for the selection of the most effective inflammatory stimulus. Subsequently, explants challenged with TNFα+IL-1β were exposed to CM, consisting of a pool of concentrated supernatants from 72-h cultured ASCs, in order to evaluate its effect on cartilage catabolism and inflammation.</p></div><div><h3>Results</h3><p>The 3-day treatment with both 10ng/ml TNFα and 1ng/ml IL-1β significantly increased MMP activity and NO release, without affecting GAG release. The addition of CM significantly downregulated the abnormal MMP activity induced by the inflammatory stimuli, while also mildly reducing <em>MMP3</em>, <em>MMP13,</em> and <em>PTGS2</em> gene expression. Finally, <em>SOX9</em> and <em>COL2A1</em> were downregulated by the cytokines, and further decreased by CM.</p></div><div><h3>Conclusion</h3><p>The proposed cartilage explant model offers encouraging evidence of the therapeutic potential of ASC-derived CM against OA, and it could serve as a convenient <em>ex vivo</em> platform for drug screening.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 346-353"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001172/pdfft?md5=841c56d28c32eec00f0695ae0cfe5229&pid=1-s2.0-S2352320424001172-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141483235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The application of retinal organoids in ophthalmic regenerative medicine: A mini-review","authors":"Xinmei Lan ,&nbsp;Huixia Jiang ,&nbsp;Qian Wang,&nbsp;Qin Shiqi,&nbsp;Yu Xiong","doi":"10.1016/j.reth.2024.06.013","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.013","url":null,"abstract":"<div><p>Retinal organoids are three-dimensional (3D) microscopic tissues that are induced and differentiated from stem cells or progenitor cells in vitro and have a highly similar structure to the retina. With the optimization and development of 3D retinal culture system and the improvement of induced differentiation technology, retinal organoids have broad application prospects in retinal development, regenerative medicine, biomaterial evaluation, disease mechanism investigation, and drug screening. In this review we summarize recent development of retinal organoids and their applications in ophthalmic regenerative medicine. In particular, we highlight the promise and challenges in the use of retinal organoids in disease modeling and drug discovery.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 382-386"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001202/pdfft?md5=1f3f4b63c5efa7ae5b653d1622f58849&pid=1-s2.0-S2352320424001202-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141484341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustainably cultured coral scaffold supports human bone marrow mesenchymal stromal cell osteogenesis","authors":"Chiara Gentili ,&nbsp;Maria Elisabetta Federica Palamà ,&nbsp;Gillian Sexton ,&nbsp;Sophie Maybury ,&nbsp;Megan Shanahan ,&nbsp;Yeyetunde Yvonne Omowunmi-Kayode ,&nbsp;James Martin ,&nbsp;Martin Johnson ,&nbsp;Kerry Thompson ,&nbsp;Owen Clarkin ,&nbsp;Cynthia M. Coleman","doi":"10.1016/j.reth.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.002","url":null,"abstract":"<div><p>The current gold standard grafting material is autologous bone due to its osteoinductive and osteoconductive properties. Autograft harvesting results in donors site morbidity. Coral scaffolds offer a natural autograft alternative, sharing the density and porosity of human bone. This study investigated the biocompatibility and osteogenic potential of a novel, sustainably grown <em>Pocillopora</em> scaffold with human bone marrow-derived mesenchymal stromal cells (MSCs). The coral-derived scaffold displays a highly textured topography, with concavities of uniform size and a high calcium carbonate content. Large scaffold samples exhibit compressive and diametral tensile strengths in the range of trabecular bone, with strengths likely increasing for smaller particulate samples. Following the <em>in vitro</em> seeding of MSCs adjacent to the scaffold, the MSCs remained viable, continued proliferating and metabolising, demonstrating biocompatibility. The seeded MSCs densely covered the coral scaffold with organized, aligned cultures with a fibroblastic morphology. <em>In vivo</em> coral scaffolds with MSCs supported earlier bone and blood vessel formation as compared to control constructs containing TCP-HA and MSCs. This work characterized a novel, sustainably grown coral scaffold that was biocompatible with MSCs and supports their <em>in vivo</em> osteogenic differentiation, advancing the current repertoire of biomaterials for bone grafting.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 366-381"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001093/pdfft?md5=27f752fdc8eedb841ee4565a44c1c527&pid=1-s2.0-S2352320424001093-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141484387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attitudes of patients with IVF/ICSI toward human embryo in vitro culture beyond 14 days","authors":"Yukitaka Kiya ,&nbsp;Saori Watanabe ,&nbsp;Kana Harada ,&nbsp;Hideki Yui ,&nbsp;Yoshimi Yashiro ,&nbsp;Kaori Muto","doi":"10.1016/j.reth.2024.09.005","DOIUrl":"10.1016/j.reth.2024.09.005","url":null,"abstract":"<div><p>When the International Society for Stem Cell Research revised its 2021 guidelines, it reversed its ban on the <em>in vitro</em> culture of human embryos beyond 14 days. However, despite widespread recognition of the importance of public debate on embryo research, it remains unclear how patients who have undergone in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) perceive this change in the guidelines. Three focus group interviews were conducted with IVF/ICSI patients to understand their opinions on extending the in vitro culture of human embryos beyond 14 days. Thematic analysis revealed a primarily favorable attitude toward the extension of in vitro embryo culture, identifying six reasons for this positive perspective. However, two reasons for negative attitudes were identified, along with some concerns that need to be addressed. To facilitate an open discussion, the following suggestions were made to the government and scientific community. The government and scientific community should provide sufficient knowledge to IVF/ICSI patients about research before discussions. It's important to consider diverse views on embryo models, including distrust and resistance. Ensuring IVF/ICSI patients' psychological safety is essential. “Public conversations” with citizens, including IVF/ICSI patients, should be promoted, and their opinions should be considered as part of a broader public spectrum.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 831-836"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001664/pdfft?md5=cb2954e50dcb6360aac3c414c5ff6288&pid=1-s2.0-S2352320424001664-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteogenic effects and safety of human induced pluripotent stem cell-derived megakaryocytes and platelets produced on a clinical scale","authors":"Takahito Arai ,&nbsp;Yasuhiro Shiga ,&nbsp;Michiaki Mukai ,&nbsp;Naoya Takayama ,&nbsp;Susumu Tashiro ,&nbsp;Ikuko Tajiri ,&nbsp;Kentaro Kosaka ,&nbsp;Masashi Sato ,&nbsp;Sou Nakamura ,&nbsp;Haruki Okamoto ,&nbsp;Seiji Kimura ,&nbsp;Kazuhide Inage ,&nbsp;Miyako Suzuki-Narita ,&nbsp;Yawara Eguchi ,&nbsp;Sumihisa Orita ,&nbsp;Koji Eto ,&nbsp;Seiji Ohtori","doi":"10.1016/j.reth.2024.09.012","DOIUrl":"10.1016/j.reth.2024.09.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Platelet-rich plasma obtained by centrifuging peripheral blood can promote osteogenesis owing to its abundant growth factors but has drawbacks, including rapid growth factor loss and inconsistent effects depending on donor factors. To overcome these issues, we were the first in the world to use freeze-dried human induced pluripotent stem cell-derived megakaryocytes and platelets (S-FD-iMPs) and found that they have osteogenesis-promoting effects. Since turbulence was found to activate platelet biogenesis and iPS cell-derived platelets can now be produced on a clinical scale by a device called VerMES, this study examined the osteogenesis-promoting effect and safety of clinical-scale FD-iMP (V-FD-iMPs) for future human clinical application.</div></div><div><h3>Method</h3><div>We administered either S-FD-iMPs, V-FD-iMPs, or saline along with artificial bone to the lumbar spine of 8-week-old male Sprague–Dawley rats (n = 4 each) and evaluated bone formation by computed tomography (CT) and pathology. Next, we administered V-FD-iMPs or saline along with artificial bone to the lumber spines of 5-week-old male New Zealand White rabbits (n = 4 each) and evaluated the bone formation by CT and pathology. Rats (n = 10) and rabbits (n = 6) that received artificial bone and V-FD-iMPs in the lumbar spine were also observed for 6 months for adverse events, including infection, tumor formation, and death.</div></div><div><h3>Results</h3><div>Both V-FD-iMPs and S-FD-iMPs significantly enhanced osteogenesis in the lumber spines of rats in comparison with the controls 8 weeks postoperatively, with no significant differences between them. Furthermore, V-FD-iMPs vigorously promoted osteogenesis in the lumber spines of rabbits 8 weeks postoperatively. In rats and rabbits, V-FD-iMPs showed no adverse effects, including infection, tumor formation, and death, over 6 months.</div></div><div><h3>Conclusion</h3><div>These results suggest that V-FD-iMPs promote safe osteogenesis.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 850-858"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}