Regenerative Therapy最新文献

{"title":"Multimodal mechanisms of platelet-rich plasma in bone defect repair: Angiogenesis, inflammation modulation, and metabolic regulation","authors":"Junjie Chen ,&nbsp;Bo Liu ,&nbsp;Jiayang He ,&nbsp;Yuhao Wei ,&nbsp;Yuhan He ,&nbsp;Hang Zhou ,&nbsp;Zhiqiang Zhang ,&nbsp;Yiwen Weng ,&nbsp;Ming Cheng","doi":"10.1016/j.reth.2025.09.007","DOIUrl":"10.1016/j.reth.2025.09.007","url":null,"abstract":"<div><div>Bone defect is the loss of bone tissue due to trauma, fracture, infection, etc. This loss may lead to non-union of fracture, bone defect or bone deficiency, which seriously affects the patient's quality of life and even leads to dysfunction and disability. Although surgical repair is a common treatment modality, the surgical procedure is complicated, with a long postoperative recovery period and certain surgical risks, such as infection and bleeding. Platelet-rich plasma (PRP), as a novel therapeutic approach, has demonstrated remarkable potential in bone defect repair. PRP is rich in growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), etc., and can have a beneficial effect on bone defect repair through various mechanisms, such as the release of growth factors, the promotion of angiogenesis, the inhibition of inflammatory response, and the recruitment of activated cells and other mechanisms, which play a positive role in the repair of bone defects and provide strong support for the regeneration and repair of bone tissue.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 920-932"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The umbilical cord blood exosome MFG-E8 alleviates hypoxic-ischemic encephalopathy brain injury in neonatal rats by restoring autophagy flux and inhibiting ferroptosis through GSK3β/β-catenin signaling","authors":"Menghua Zhao ,&nbsp;Yizhong Wu ,&nbsp;Li Huang ,&nbsp;Juanmei Wang ,&nbsp;Aimin Zhang","doi":"10.1016/j.reth.2025.06.016","DOIUrl":"10.1016/j.reth.2025.06.016","url":null,"abstract":"<div><h3>Background</h3><div>Recent studies have revealed importance of human umbilical cord blood (HUCB)-derived exosomes (HUCB-Exo) in central nervous system diseases, but the role of HUCB-Exo in hypoxic-ischemic encephalopathy (HIE) remains unclear. This study aims to explore the mechanisms of HUCB-Exo in HIE.</div></div><div><h3>Methods</h3><div>HIE models were constructed in 7-day-old neonatal rats using classical Rice-Vannucci modeling, and SH-SY5Y cells were induced by oxygen-glucose deprivation/reperfusion (OGD/R) injury, followed by intervention with HUCB and HUBC-Exo, either non-transfected or transfected with si-NC/si-MFG-E8.</div></div><div><h3>Results</h3><div>HUBC-Exo decreased cerebral infarct size and cerebral water content in HIE neonatal rats and improved short-term and long-term neurological function. HUBC-Exo down-regulated Beclin1, ATG7, and LC3 II/I expression, while promoting p62 expression in HIE neonatal rats. After HUBC-Exo treatment, NCOA4 and ACSL4 expression in HIE neonatal rats decreased, while FTH1, SLC7A11, and GPX4 expression were increased. In addition, HUBC-Exo decreased Fe²⁺, MDA, and ROS levels in HIE neonatal rats. Similarly, these <em>in vivo</em> results were observed <em>in vitro</em>. HUBC-Exo inhibited autophagy and ferroptosis in OGD/R-induced SH-SY5Y cells, and MFG-E8 silencing interrupted HUBC-Exo action. Further results showed that HUBC-Exo-derived MFG-E8 promoted p-GSK3β/GSK3β and Active-β-catenin/β-catenin levels in OGD/R-induced SH-SY5Y cells. Importantly, the GSK3β agonist LiCl revoked the promotion of HUBC-Exo^si-MFG-E8 on autophagy and ferroptosis in OGD/R-induced SH-SY5Y cells. HUBC-Exo MFG-E8 inhibited autophagy and ferroptosis, thereby alleviating brain damage in HIE neonatal rats.</div></div><div><h3>Conclusion</h3><div>Our results suggested that HUBC-Exo-transmitted MFG-E8 inhibited autophagy and ferroptosis through GSK3β/β-catenin signaling, thereby alleviating brain injury in HIE neonatal rats, which provided a new idea for treating HIE.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 321-332"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The research landscape and trends of dental pulp stem cell studies (2010–2025): A bibliometric analysis","authors":"Yu Zheng ,&nbsp;Zhe Tang ,&nbsp;Lu Li ,&nbsp;Zheng Li","doi":"10.1016/j.reth.2025.10.021","DOIUrl":"10.1016/j.reth.2025.10.021","url":null,"abstract":"<div><h3>Background</h3><div>Dental pulp stem cells (DPSCs) have emerged as a promising therapeutic modality in regenerative medicine, yet systematic bibliometric evaluation of global research landscape has been lacking.</div></div><div><h3>Methods</h3><div>Publications from 2010 to 2025 were retrieved from Web of Science Core Collection. After screening, 4599 English-language articles and reviews were analyzed using VOSviewer, CiteSpace, and Bibliometrix for publication trends, geographic distribution, author collaboration, journal characteristics, citation networks, and keyword co-occurrence.</div></div><div><h3>Results</h3><div>Global DPSC research demonstrated sustained growth, with annual publications increasing from 97 in 2010 to 464 in 2024. China (32.6 %), United States (15.9 %), and Japan (9.9 %) contributed over half the global output, though U.S. publications achieved higher citation impact. Sichuan University, Sun Yat-sen University, and Capital Medical University ranked highest in productivity. Author collaboration revealed interconnected clusters led by pioneering researchers including Shi Songtao, Nakashima Misako, and Nor Jacques E. Journal of Endodontics was the leading publishing platform, while co-citation analysis highlighted intellectual influence of multidisciplinary journals including Stem Cells, Biomaterials, and PNAS. Keyword analyses demonstrated thematic evolution from cellular characterization toward translational applications, with emerging frontiers focusing on extracellular vesicles, exosomes, and cell-free therapeutic strategies.</div></div><div><h3>Conclusions</h3><div>DPSC research has evolved into a mature, internationally collaborative scientific discipline successfully bridging fundamental biology and clinical application. A pivotal paradigm shift from cell-centric to cell-free therapies is currently underway. Future breakthroughs will likely depend on harnessing the DPSC secretome and developing intelligent, clinically viable regenerative strategies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 1013-1023"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-response immunomodulatory effects of Mesenchymal stem cell-derived culture-conditioned media in acute Graft-versus-Host Disease","authors":"Mohini Mendiratta ,&nbsp;Meenakshi Mendiratta ,&nbsp;Sujata Mohanty ,&nbsp;Sandeep Rai ,&nbsp;Ritu Gupta ,&nbsp;Vatsla Dadhwal ,&nbsp;Sameer Bakhshi ,&nbsp;Deepam Pushpam ,&nbsp;Mukul Aggarwal ,&nbsp;Aditya Kumar Gupta ,&nbsp;Ranjit Kumar Sahoo","doi":"10.1016/j.reth.2025.10.001","DOIUrl":"10.1016/j.reth.2025.10.001","url":null,"abstract":"<div><h3>Background</h3><div>Mesenchymal stem cell-based therapy faces challenges that have driven interest in MSCs-derived culture-conditioned media (CCM) as a cell-free alternative. Our study aims to optimize the dose and collection timing of CCM to enhance its therapeutic efficacy in aGVHD, while also standardizing co-culture conditions for CD3⁺ T-cell interaction with CCM.</div></div><div><h3>Material and methods</h3><div>Human MSCs were isolated from BM and WJ and subsequently preconditioned under hypoxic conditions (1 % O₂) for 24 h in a tri-gas incubator. Culture-conditioned media (CCM) were collected from both naive (MSCs) and hypoxia-preconditioned MSCs (MSCs^HYP) at 24, 48, and 72 h and filtered using a 0.2 μm membrane filter. CD3⁺ T-cell were isolated from PBMNCs derived from aGVHD patients. These T-cell were co-cultured at varying densities (2∗10⁶, 5∗10⁶, and 10∗10⁶ cells/ml) with different concentrations of CCM (25 %, 50 %, and 100 %), and cell proliferation was assessed using the MTS assay. Furthermore, CD3⁺ T-cell proliferation and activation status were evaluated in a 2D co-culture model of CD3⁺ T-cell and CCM using flow cytometry.</div></div><div><h3>Results</h3><div>Our findings revealed that CCM collected at 48 h, at a 50 % concentration, exerted the most pronounced inhibitory effect on CD3⁺ T-cell proliferation, particularly at a density of 5∗10⁶ cells/ml, irrespective of the MSCs source. Hypoxia preconditioning significantly enhanced the immunomodulatory effects, with WJ-MSCs^HYP-CCM demonstrating superior efficacy in suppressing T-cell proliferation, increasing the CD4⁺/CD8⁺ T-cell ratio, and reducing CD4⁺ T-cell activation compared to BM-MSCs^HYP-CCM.</div></div><div><h3>Conclusion</h3><div>These results emphasize the critical role of optimizing CCM collection timing and concentration to maximize therapeutic potential. Our study paves the way for the development of standardized, scalable, and effective cell-free therapies for aGVHD.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 868-874"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tangeretin suppresses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling","authors":"Tengfei Wu,&nbsp;Fang Wang,&nbsp;Changqing Ai,&nbsp;Li Li,&nbsp;Fan Wu","doi":"10.1016/j.reth.2025.04.019","DOIUrl":"10.1016/j.reth.2025.04.019","url":null,"abstract":"<div><h3>Background</h3><div>Postmenopausal osteoporosis is characterized by osteoclast differentiation and bone loss. Tangeretin (TGN) is a natural product that possesses multiple pharmacological properties. However, its specific function in postmenopausal osteoporosis deserves further exploration.</div></div><div><h3>Methods</h3><div>The <em>in vitro</em> and <em>in vivo</em> models of postmenopausal osteoporosis were established by using BMMs stimulated with M-CSF and RANKL and mice receiving ovariectomized (OVX) operation. Osteoclast-specific gene expression was determined by RT-qPCR. The protein level was detected by Western blotting. H&amp;E staining was performed to observe the pathological changes in murine distal femurs.</div></div><div><h3>Results</h3><div>For <em>in vitro</em> study, TGN did not affect cell viability but downregulated RANKL-stimulated osteoclast-specific gene expression. For <em>in vivo</em> study, TGN not only alleviated OVX-triggered pathological alterations of femur tissue, but also effectively inhibited proteoglycan loss and cartilage injury induced by OVX in the femurs of mice. Additionally, TGN prevented osteoclastogenesis in OVX mice by downregulating TRAP activity and osteoclast-specific gene expression. Mechanistically, TGN significantly inhibited the activation of Notch signaling via the downregulation of Notch-1, Notch-2, Notch-3, Jagged1, Hes-1, and Hey-1 protein levels <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>TGN represses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 136-143"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutic potential of neuroglobin-overexpressing human neural stem cells in a photothrombosis model","authors":"Eun-Jung Yoon ,&nbsp;Jiwon Jeong ,&nbsp;Jisu An ,&nbsp;Yunseo Choi ,&nbsp;Dongsun Park","doi":"10.1016/j.reth.2025.07.013","DOIUrl":"10.1016/j.reth.2025.07.013","url":null,"abstract":"<div><h3>Background</h3><div>Neuroglobin (NGB) is an oxygen-binding protein with neuroprotective properties under hypoxic and ischemic conditions. It promotes cell survival, reduces oxidative stress, and activates survival-related signaling pathways. This study aimed to evaluate whether overexpression of NGB in human neural stem cells (F3.NGB) could enhance their regenerative potential and therapeutic efficacy in photothrombosis model.</div></div><div><h3>Methods</h3><div>F3 cells were genetically engineered to overexpress NGB. In vitro proliferation and migration were assessed using CCK-8, colony forming, and scratch-based wound healing assays. In vivo, a photothrombosis-induced stroke model was used to evaluate infarct volume, transplanted cell migration and differentiation, and activation of proliferation-related signaling pathways following intravenous transplantation of F3.NGB cells.</div></div><div><h3>Results</h3><div>NGB overexpression significantly enhanced the proliferative capacity of F3 cells, and F3.NGB cells promoted N2A cell proliferation and actively migrated in co-culture conditions. In vivo, transplantation of F3.NGB cells resulted in a significant reduction in infarct volume compared with that in the controls. Western blot analysis showed increased activation of PI3K/AKT, mTOR, and ERK signaling pathways, with decreased PTEN expression. Immunohistochemical staining confirmed that F3.NGB cells migrated to the infarcted region, differentiated into neurons and astrocytes, and showed strong Ki67 positivity, indicating active proliferation at the injury site.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that F3.NGB cells reduce ischemic brain damage primarily by enhancing cell proliferation, and also migrate to the injury site and undergo differentiation into neurons or astrocytes. These results suggest that F3.NGB cell-based therapy may contribute to the development of advanced regenerative strategies for the treatment of ischemic stroke.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 515-524"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant production of canine vitronectin for optimizing the culture of canine induced pluripotent stem cells","authors":"Kohei Shishida ,&nbsp;Yui Ikuta ,&nbsp;Hiroko Sugisaki ,&nbsp;Kazuto Kimura ,&nbsp;Jun Katahira ,&nbsp;Masaya Tsukamoto ,&nbsp;Shingo Hatoya","doi":"10.1016/j.reth.2025.09.002","DOIUrl":"10.1016/j.reth.2025.09.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Canine induced pluripotent stem cells (ciPSCs) have attracted attention as valuable tools in veterinary regenerative medicine and disease modeling. Feeder-free culture of ciPSCs using iMatrix-511 has become feasible. Since the choice of extracellular matrix (ECM) has been shown to significantly affect not only the maintenance of pluripotency but also the efficiency of directed differentiation, systematic evaluation of multiple ECM substrates is considered important in ciPSC culture as well. Furthermore, considering future clinical applications, it is essential to establish a xeno-free culture system. Vitronectin (VTN) is a protein that can be easily expressed as a recombinant product in <em>Escherichia coli</em>, making it suitable for scalable ECM production. In this study, we generated recombinant canine-derived VTN and evaluated its effects on ciPSCs in comparison with human-derived ECM substrates.</div></div><div><h3>Methods</h3><div>In this study, we generated recombinant full-length and N-terminally truncated forms of canine vitronectin (cVTN and cVTN-N) using a bacterial expression system. These substrates, along with established human-derived ECM proteins including iMatrix-511, hVTN, and hVTN-N, were evaluated for their ability to support ciPSC adhesion, proliferation, and the maintenance of pluripotency and differentiation potential. Pluripotency and differentiation capacity were assessed using immunostaining and gene expression analysis.</div></div><div><h3>Results</h3><div>Both cVTN and cVTN-N demonstrated support for ciPSC attachment and long-term proliferation at levels comparable to those of human-derived ECM substrates. ciPSCs cultured on cVTN or cVTN-N maintained high expression levels of pluripotency markers; in particular, cVTN significantly enhanced SOX2 expression, while cVTN-N was associated with reduced mesodermal marker expression. Efficient EBs formation and trilineage differentiation were achieved on all tested substrates, with only minor differences in lineage marker expression among groups.</div></div><div><h3>Conclusions</h3><div>Recombinant canine-derived VTN were shown to function as an effective, species-matched substrate for ciPSC culture, exhibiting comparable performance to human-derived ECM proteins. These results suggest that canine-derived VTN enables stable proliferation and maintenance of pluripotency in ciPSCs, providing a promising platform for future research in canine regenerative medicine.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 751-759"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome-derived bile acids as endogenous regenerative mediators in liver repair","authors":"Surya Nath Pandey ,&nbsp;Kavita Goyal ,&nbsp;Mohit Rana ,&nbsp;Soumya V. Menon ,&nbsp;Subhashree Ray ,&nbsp;Haider Ali ,&nbsp;Popat S. Kumbhar ,&nbsp;John Disouza ,&nbsp;Sachin Kumar Singh ,&nbsp;Gaurav Gupta ,&nbsp;Ling Shing Wong ,&nbsp;Vinoth Kumarasamy ,&nbsp;Vetriselvan Subramaniyan","doi":"10.1016/j.reth.2025.08.011","DOIUrl":"10.1016/j.reth.2025.08.011","url":null,"abstract":"<div><div>The liver's extraordinary capacity for self-repair is often compromised by chronic injury, fibrosis, or extensive resection, creating an urgent need for innovative regenerative therapies to restore liver function. Emerging evidence suggests that microbiome-derived bile acid metabolites are potent endogenous mediators of hepatic regeneration. Beyond their canonical role in lipid emulsification, these chemically diverse molecules engage nuclear and membrane receptors, most notably the farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), to stimulate hepatocyte proliferation, modulate inflammatory responses, and reactivate quiescent progenitor cells. In this review, we integrate mechanistic insights from partial hepatectomy, germ-free, and antibiotic-treated animal models with early clinical observations to illuminate how primary and secondary bile acids orchestrate cell cycle progression, cytokine balance, and extracellular matrix remodeling. We then examined the therapeutic landscape, from synthetic FXR/TGR5 agonists to live-biotherapeutic approaches, genetically modified probiotic strains, and fecal microbiota transplantation. We highlight the preliminary indicators of efficacy and challenges in manufacturing consistency, safety profiling, and regulatory classification. We address the interindividual variability in microbiome composition, potential biomarkers such as serum FGF19, imaging-based measures of functional liver mass, and considerations for optimal trial design. This is the first comprehensive review to frame microbiome-driven bile acids as direct modulators of liver regeneration and chart a coherent translational development pathway. By integrating stem cell biology, hepatology, microbiology, and bioengineering perspectives, we demonstrate the underexplored therapeutic potential of these approaches to transform the future of hepatic repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 681-690"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Advances in sciatic nerve regeneration: A review of contemporary techniques” [Regen Ther, Volume 29C, (June 2025), 563–574]","authors":"Sardar Ali ,&nbsp;Ming Sun ,&nbsp;Muhammad Nadeem Khan ,&nbsp;Fang Qiang","doi":"10.1016/j.reth.2025.08.013","DOIUrl":"10.1016/j.reth.2025.08.013","url":null,"abstract":"","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Page 691"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome-based profiles of airborne bacteria to support microbial risk assessment in cleanroom environments","authors":"Mitsuru Mizuno ,&nbsp;Yusuke Ogata ,&nbsp;Yuto Nishihara ,&nbsp;Miwako Nishio ,&nbsp;Hisako Katano ,&nbsp;Ichiro Sekiya","doi":"10.1016/j.reth.2025.10.019","DOIUrl":"10.1016/j.reth.2025.10.019","url":null,"abstract":"<div><h3>Introduction</h3><div>Maintaining aseptic conditions is essential for cell product processing, as sterilization cannot be applied to living cells. Conventional environmental monitoring relies on particle counts and culture-based colony-forming unit measurements. These indicators fail to capture much of the diversity and provenance of airborne microbes because many taxa are nonculturable or require growth conditions not supported by standard culture media. Therefore, comprehensive DNA-based microbiome analysis is critical for evaluating microbial risks that conventional methods may overlook; however, such studies remain limited in cleanroom settings. This study aimed to comprehensively visualize the structure of airborne microbial communities in cleanroom environments and clarify microbial risks that cannot be fully captured by particle counts or culture-based methods.</div></div><div><h3>Methods</h3><div>We collected airborne bacterial DNA from cleanrooms with environmental Grades B, C, and D using a high-volume air sampler. The DNA was extracted and analyzed via 16S rRNA gene amplicon sequencing targeting the V3–V4 regions. Bioinformatic analysis was performed using the QIIME2 pipeline, and microbial diversity was assessed using alpha and beta diversity indices. Abundant taxa were categorized based on their likely origin (environment- or skin-derived), and their distributions were examined in relation to facility management practices.</div></div><div><h3>Results</h3><div>Analysis revealed the consistent detection of skin-associated bacteria, such as <em>Cutibacterium</em> and <em>Corynebacterium</em>, and environmental bacteria, including <em>Bacillus</em> and <em>Paracoccus</em>, across all cleanroom grades. Alpha- and beta-diversities exhibited no significant differences among the grades. However, temporary and irregular increases in skin-derived bacteria indicated operator-related non-persistent contamination. This interpretation was supported by skewness and kurtosis analyses, which indicated occasional but noticeable shifts in microbial abundance, particularly in high-grade cleanroom environments.</div></div><div><h3>Conclusions</h3><div>This study demonstrates the limitations of conventional culture-based monitoring and underscores the value of DNA-based approaches for characterizing airborne microbial communities in cleanrooms. The detection of temporary increases in skin-associated bacteria indicates that operator-related contamination can occur even under stringent environmental conditions. These findings support the development of integrated monitoring strategies that can capture both the composition and temporal fluctuations of airborne microbiota to enhance microbial risk assessment.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 991-998"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}