Regenerative Therapy最新文献

{"title":"Erratum to “Which trajectory should we choose? — Defining safe entry–target pathways and underlying femoral morphology for bone marrow injection in osteonecrosis of the femoral head” [Regen Ther 31C(2026) 101084]","authors":"Ken Tashiro , Yasuhiro Homma , Yuto Kawamura , Ryuji Okuno , Eiji Iwasaki , Fumihiro Mukasa , Koju Hayashi , Taiji Watari , Tomonori Baba , Muneaki Ishijima","doi":"10.1016/j.reth.2026.101088","DOIUrl":"10.1016/j.reth.2026.101088","url":null,"abstract":"","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"32 ","pages":"Article 101088"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148183802","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 “Kidney organoid vascularization: current advancements in the field” [Regen Ther 32C (2026) 101087]","authors":"Hiroki Shioda , Tien-Hsiang Tang , Irina Raykhel , Yasuyuki Sakai , Masaki Nishikawa","doi":"10.1016/j.reth.2026.101115","DOIUrl":"10.1016/j.reth.2026.101115","url":null,"abstract":"","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"32 ","pages":"Article 101115"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148183803","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":"Unapproved regenerative medicine for spinal cord injury in Japan","authors":"Yuichiro Ukon ,&nbsp;Hideyuki Hakui ,&nbsp;Satoshi Hosoya ,&nbsp;Kazuki Morita ,&nbsp;Hirokazu Mae ,&nbsp;Yuya Kanie ,&nbsp;Masayuki Furuya ,&nbsp;Takahito Fujimori ,&nbsp;Kiyoshi Okada ,&nbsp;Akira Myoui ,&nbsp;Seiji Okada","doi":"10.1016/j.reth.2026.101132","DOIUrl":"10.1016/j.reth.2026.101132","url":null,"abstract":"<div><div>This study presented an overview of unapproved regenerative medicine for spinal cord injury (SCI) in Japan under the Act on the Safety of Regenerative Medicine. In total, 41 non-research regenerative medicine provision plans were identified. Three plans (7%) specified administration exclusively during the chronic phase, whereas remaining plans did not state the period. Most therapies used adipose-derived (68%) or bone marrow-derived (32%) mesenchymal stem cells. The most common administration route was intravenous (71%), followed by intrathecal (27%). Culture periods were typically around four weeks, and the most frequently administered cell dose was 1.0 × 10⁸ cells, although variability existed across plans. The mean treatment price was 14,100 USD. Clinical research conducted under the RM Act and approved regenerative medical products primarily targeted subacute SCI, using standardized cell sources, dosing strategies, and safety evaluations. These findings demonstrate marked heterogeneity and limited scientific standardization among unapproved regenerative medicine for SCI in Japan.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"32 ","pages":"Article 101132"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157270","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":"Isolation of small extracellular vesicles by interacting with inorganic surface","authors":"Satoe Obuchi ,&nbsp;Masamune Morita ,&nbsp;Goshi Kuno ,&nbsp;Toshifumi Mogami ,&nbsp;Tomohiro Shuno ,&nbsp;Yuto Ito ,&nbsp;Makoto Miyagishi ,&nbsp;Yoshio Ohba ,&nbsp;Akiko Kuramochi ,&nbsp;Yuji Teramura","doi":"10.1016/j.reth.2026.101063","DOIUrl":"10.1016/j.reth.2026.101063","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) have great potential as diagnostic and therapeutic tools because they are important mediators of intercellular communication. Although several EV isolation methods have been developed, efficient and selective isolation remains challenging owing to the presence of coexisting proteins and other EV subtypes. Herein, we report an EV purification method using inorganic materials composed of calcium phosphate and calcium carbonate combining with magnetic particles, wherein EVs are captured to phosphate and carbonate groups via surface calcium residues through metal coordinate bonds with their negatively charged phospholipids of EVs.</div></div><div><h3>Methods</h3><div>Cultured supernatants from three cell lines (HEK293T and cancer cells, MCF7 and PC3) were subjected to sequential centrifugation and filtration to remove cell debris and components smaller than 100 kDa, followed by purification using our inorganic material-based method. For comparison, conventional approaches, including polymer precipitation and phosphatidylserine (PS)-specific binding protein-based purification, were used. Purified EVs were characterized based on total protein content, surface marker expression (CD63 and CD81), and miRNA levels.</div></div><div><h3>Results</h3><div>The results revealed that our method enriched EVs with higher surface marker expression and miRNA content more efficiently than other approaches, while maintaining EV integrity and minimizing protein contamination. Although EVs were isolated from the same cell line, their compositions differed, indicating that the purification method should be carefully selected.</div></div><div><h3>Conclusion</h3><div>Thus, our inorganic material-mediated approach provides an effective platform for small extracellular vesicle (sEV) isolation, with potential applications in basic research and clinical diagnostics.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101063"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976702","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":"Genomic analysis of dental pulp mesenchymal stromal cells for therapeutic applications","authors":"Kunio Hirai ,&nbsp;Yuko Nitahara-Kasahara ,&nbsp;Yuko Okamoto ,&nbsp;Noriko Sangu-Miyamoto ,&nbsp;Yuko Aizen ,&nbsp;Atsushi Watanabe ,&nbsp;Takashi Okada","doi":"10.1016/j.reth.2026.101080","DOIUrl":"10.1016/j.reth.2026.101080","url":null,"abstract":"<div><h3>Introduction</h3><div>Changes in cell characteristics and the accumulation of gene mutations during expansion culture present significant challenges for the clinical translation of stem cell transplantation technologies. Reduced cell quality may lead to diminished therapeutic efficacy and unexpected cellular dysfunction after transplantation. Mesenchymal stromal cells (MSCs), including dental pulp stromal cells (DPSCs), are promising candidates for clinical application because of their multipotent differentiation capacity, immunosuppressive properties, and proliferative potential. However, robust strategies to assess genomic stability during large-scale cell preparation remain insufficient.</div></div><div><h3>Methods</h3><div>DPSCs derived from healthy donors maintained safety profiles and exhibited delayed senescence even after more than 10 passages under large-scale expansion conditions. To evaluate genomic stability, DPSCs derived from healthy individuals and patients with type 1 diabetes mellitus were analyzed after successive passages. Copy number variations (CNVs) were assessed using CytoScan, and disease-related gene mutations were analyzed using the TruSight One Sequencing Panel.</div></div><div><h3>Results</h3><div>During long-term expansion, increases in chromosomal CNVs and <em>de novo</em> gene mutations were observed at earlier stages in cells showing reduced proliferative capacity, depending on donor characteristics. We identified mutation accumulation patterns and genes that were particularly susceptible to substitutions or insertions/deletions during expansion, indicating inter-donor variability in genomic alterations in DPSCs.</div></div><div><h3>Conclusion</h3><div>This work addresses a critical bottleneck in stem cell therapy by integrating genomic risk profiling into early-stage cell quality assessment, enabling safer and more reliable cell product development. Furthermore, our findings highlight the feasibility of applying medical genomic tools to preemptively identify putative high-risk cell populations during stem cell manufacturing, thereby providing a practical framework for improving the safety and consistency of cell-based transplantation therapies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101080"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348894","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":"Can cell-based therapies bridge the gap between research and reality in the treatment of myocarditis? A systematic review and meta-analysis","authors":"Ulugbek Yakhshimurodov ,&nbsp;Kizuku Yamashita ,&nbsp;Sho Komukai ,&nbsp;Bekzod Isomitdinov ,&nbsp;Takuji Kawamura ,&nbsp;Shunsuke Saito ,&nbsp;Shigeru Miyagawa","doi":"10.1016/j.reth.2026.101077","DOIUrl":"10.1016/j.reth.2026.101077","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Myocarditis is a non-ischaemic myocardial injury caused by infectious agents, immune-mediated diseases, cardiotoxic drugs, and vaccines. Treatment options are largely supportive, with emphasis on close monitoring, exclusion of other diseases explaining symptoms, adherence to heart failure treatment recommendations, and consideration of etiology-directed interventions, if applicable, such as antiviral or immunosuppressive agents, steroids, discontinuation of antineoplastic therapy, and strategies to increase left ventricular (LV) ejection fraction (LVEF). In this context, cell-based therapies (CBTs) have emerged as a new therapeutic strategy and were believed to fill this gap. However, results were inconsistent across studies, which necessitates the need for rigorous systematic reviews to analyze available evidence comprehensively.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The review protocol was registered on the PROSPERO website, and the study was conducted in accordance with PRISMA regulations. Searches were conducted in Embase, CINAHL Plus via EBSCO host, Web of Science, Scopus, and PubMed. A total of 60 original papers published between 2004 and 2022 in 48 peer-reviewed journals were included in the meta-analysis to determine the efficacy of CBTs on the LV fractional shortening (LVFS), LVEF, capillary density (CD), inflammatory cell infiltration rate (ICIR), and fibrotic area (FA). The risk of bias (RoB) and study quality were assessed using the SYRCLE RoB tool and CAMARADES checklist, respectively. As the preliminary assessment indicated substantial heterogeneity among the included studies, a random-effects model was applied to pool effect sizes. Subgroup analyses were performed to explore potential sources of heterogeneity across studies. Publication bias was assessed by visual inspection of funnel plots for asymmetry and statistically evaluated using Egger's regression test.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In total, the adapted and optimized search strategy retrieved 14,503 records from five databases. The majority of studies exhibited an unclear or high risk of bias in several domains, particularly selection bias and performance bias. Quality assessment revealed that only four studies (6.7%) were classified as high quality and four (6.7%) as low quality, while the remaining 52 studies (86.7%) were rated as moderate quality, with scores ranging from 4 to 6. CBTs improved LVFS (%) by 7.17 [95 % CI: 5.67, 8.66], LVEF (%) by 9.00 [95 % CI: 7.03, 10.97], CD (capillaries/mm&lt;sup&gt;2&lt;/sup&gt;) by 300.50 [95 % CI: 45.01, 555.99] and decreased ICIR (cells/mm&lt;sup&gt;2&lt;/sup&gt;) and FA (%) by −178.99 [95 % CI: −225.91, −132.08] and −6.04 [95 % CI: −6.83, −5.25], respectively. However, significant heterogeneity between studies was maintained at I&lt;sup&gt;2&lt;/sup&gt; = 84-99%.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Despite significant heterogeneity and moderate publication bias, the results were very encouraging, as reflected in the consis","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101077"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147356017","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":"Abnormal circ-CDK8 expression affects periodontitis development by regulating let-7b-5p/MAP4K3 signaling","authors":"Yabo Li ,&nbsp;Cailing Yang ,&nbsp;Mengdie Jin ,&nbsp;Ting Liu ,&nbsp;Changqing Yuan ,&nbsp;Jingjing Zheng","doi":"10.1016/j.reth.2026.101075","DOIUrl":"10.1016/j.reth.2026.101075","url":null,"abstract":"<div><div>Periodontitis, a chronic inflammatory disorder characterized by progressive alveolar bone loss, relies heavily on the osteogenic differentiation capacity of periodontal ligament stem cells for bone regeneration. While inflammatory conditions are known to impair this osteogenic potential, the specific regulatory mechanisms, particularly those involving circular RNAs, remain to be elucidated. This study was therefore conducted to investigate the functional role of circ-CDK8 in regulating periodontal ligament stem cells (PDLSCs) differentiation under inflammatory conditions and to elucidate its mechanism of action through the let-7b-5p/MAP4K3 pathway and associated autophagy processes. <strong>Our investigation revealed significant upregulation of circ-CDK8 in periodontitis tissues compared to healthy tissues.</strong> Using an inflammatory model with TNF-α and IL-1β stimulation, we demonstrated that circ-CDK8 suppression enhanced osteogenic differentiation while concurrently reducing autophagic activity. Mechanistic studies established that circ-CDK8 executes its regulatory function through the let-7b-5p/MAP4K3 axis, where its inhibition promotes osteogenic differentiation via autophagy modulation. These findings not only identify a novel circ-CDK8/let-7b-5p/MAP4K3 regulatory pathway in periodontitis pathogenesis but also position circ-CDK8 as a promising therapeutic target for periodontal regeneration.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101075"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187793","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":"Regulatory insights on adeno-associated virus-based gene therapies, cell- and tissue-based products, and CAR-T cell therapies: report from the 8th Asia Partnership Conference of Regenerative Medicine, April 24, 2025","authors":"Shunsuke Tominaga ,&nbsp;Yoshie Tsurumaki ,&nbsp;Yusuke Kagawa ,&nbsp;Aki Kito ,&nbsp;Masaaki Miyano ,&nbsp;Kazuhiro Ooka ,&nbsp;Srinivasan N. Kellathur ,&nbsp;Shigeaki Hayashi ,&nbsp;Masayuki Nomura","doi":"10.1016/j.reth.2026.101074","DOIUrl":"10.1016/j.reth.2026.101074","url":null,"abstract":"<div><div>The 8th Asia Partnership Conference of Regenerative Medicine (APACRM) was held in a hybrid format—both in person and online—on April 24, 2025, to advance regulatory harmonization for regenerative medicine products across Asia. Understanding the domestic regulatory guidelines and their underlying rationales within each country and region represents a crucial first step toward achieving harmonized regulation. The 8th APACRM featured open discussions and case study presentations addressing the Quality by Design (QbD) approach in gene therapy manufacturing, non-clinical evaluation of adeno-associated virus (AAV)-based gene therapy products, the product lifecycle and regulatory landscape of AAV gene therapies, and post-launch regulatory requirements for regenerative medical products. The program included presentations by industry experts and panel discussions with representatives from regulatory agencies. The latest national and regional updates on regenerative medicine were also shared. This paper summarizes the proceedings of the 8th APACRM to facilitate future dialogue and promote the dissemination of regulatory information across the field.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101074"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187794","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":"Airway basal stem cell derived extracellular vesicles promote lung repair in chronic obstructive pulmonary disease","authors":"Mengyu Zou ,&nbsp;Ying Hua ,&nbsp;Yu Zhao ,&nbsp;Suleman Shah ,&nbsp;Wei Zuo","doi":"10.1016/j.reth.2026.101068","DOIUrl":"10.1016/j.reth.2026.101068","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by irreversible damage to the airways, alveoli, and pulmonary microvasculature. As the third leading cause of death worldwide, COPD remains without effective therapies to halt or reverse structural lung damage. Regenerative approaches utilizing lung-resident stem/progenitor cells present a promising therapeutic strategy; however, the underlying molecular mechanisms remain incompletely understood. This study aimed to investigate whether the reparative effects of airway basal stem cells (BCs) in COPD are mediated, at least in part, through paracrine mechanisms involving BC-derived extracellular vesicles (BC-EVs).</div></div><div><h3>Methods</h3><div>Lineage-tracing analysis was performed to determine the involvement of endogenous BCs in epithelial repair following COPD-related lung injury. Airway BCs were isolated, expanded <em>ex vivo</em>, and transplanted into elastase-induced COPD mouse models, followed by histological evaluation and RNA-seq–based transcriptomic analysis to assess regenerative efficacy. For mechanistic studies, BC-EVs were collected from cultured BCs and characterized using transmission electron microscopy, Nano-Flow Cytometry, and Western blotting. Their biological activity was assessed by CCK-8 and tube formation assays. BC-EVs were delivered to COPD mice via nebulization, with <em>in vivo</em> imaging tracking distribution. Therapeutic efficacy was evaluated by histology and arterial blood gas analysis. Proteomic profiling was conducted to elucidate the molecular mechanisms underlying BC-EV–mediated repair.</div></div><div><h3>Results</h3><div>Lineage tracing revealed active participation of endogenous BCs in epithelial repair. Transplantation of <em>ex vivo</em>–expanded BCs significantly restored alveolar architecture and alleviated pathological manifestations in COPD mice. Nebulized BC-EVs reproduced these benefits, promoting angiogenesis, enhancing epithelial repair, and improving lung function. Proteomic analyses revealed that BC-EVs were enriched in lung development–associated proteins and activated the PI3K–Akt signaling pathway, suggesting a mechanistic basis for their regenerative capacity.</div></div><div><h3>Conclusions</h3><div>Airway basal stem cells are essential for lung epithelial regeneration, and together with their extracellular vesicles, provide a promising therapeutic strategy for COPD. The reparative effects of BCs are partially mediated by BC-EVs, which promote alveolar structure remodeling. This study delineates how BCs ameliorate COPD-induced lung injury and highlights BC-EVs as a viable cell-free therapeutic candidate with strong translational potential.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101068"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037164","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":"Wharton's jelly mesenchymal stem cell-secretome enhances skin rejuvenation via ApoA4 and SERPINH1","authors":"Na Eun Lee ,&nbsp;Jong Ik Hwang ,&nbsp;Chi Young Bang ,&nbsp;Eun Hee Kim ,&nbsp;Oh Young Bang","doi":"10.1016/j.reth.2026.101071","DOIUrl":"10.1016/j.reth.2026.101071","url":null,"abstract":"<div><h3>Introduction</h3><div>Skin aging arises from intrinsic processes and extrinsic insults (e.g., ultraviolet exposure and oxidative stress). Mesenchymal stromal cell (MSC)-derived secretome offers a cell-free approach to skin regeneration. Wharton's jelly-derived MSCs (WJ-MSCs) may outperform adipose-derived (AD-MSCs) and bone marrow-derived MSCs (BM-MSCs).</div></div><div><h3>Methods</h3><div>Secretomes from WJ-MSCs, AD-MSCs, and BM-MSCs were compared in vitro for human dermal fibroblast proliferation, scratch-wound closure, extracellular-matrix (ECM) remodeling, and type I procollagen secretion. Anti-inflammatory and antioxidant activities were assessed by IL-6, IL-1β, TNF-α, COX-2 and intracellular reactive oxygen species (ROS). Antibody arrays profiled secreted factors. An exploratory, single-arm human pilot (<em>n</em> = 21; 1-week) evaluated topical WJ-MSC secretome with paired analyses. Safety was monitored, and a separate occlusive patch test (n = 33) was conducted.</div></div><div><h3>Results</h3><div>The WJ-MSC secretome increased fibroblast proliferation, ECM remodeling, and type I procollagen, and reduced cytokines and ROS, exceeding the effects of AD-MSC and BM-MSC secretomes. Profiling highlighted apolipoprotein A4 (ApoA4) and SERPINH1 as enriched, functionally active mediators; recombinant ApoA4 and SERPINH1 enhanced fibroblast activity, collagen-related readouts, and accelerated in vitro wound closure. In the pilot study, within-subject increases in instrument-derived hydration and elasticity were observed over one week (paired tests). No treatment-related adverse events were noted. Patch testing showed no irritation (ICDRG scores all 0; non-irritant classification).</div></div><div><h3>Conclusions</h3><div>The WJ-MSC secretome demonstrated consistent in-vitro pro-regenerative, anti-inflammatory, and antioxidant activities, with ApoA4 and SERPINH1 as candidate mediators. Human findings are preliminary/exploratory and suggest potential short-term benefits that require confirmation in adequately powered, controlled trials.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101071"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181893","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}