Regenerative Therapy最新文献

{"title":"RAD51 promotes osteogenic differentiation and inhibits DNA damage in osteoporosis though regulating cGAS-STING signaling pathway","authors":"Minli Qiu ,&nbsp;Peili He ,&nbsp;Zena Chen,&nbsp;Liuzhong Zhou,&nbsp;Xinyu Wu,&nbsp;Mingcan Yang,&nbsp;Yutong Jiang,&nbsp;Jieruo Gu","doi":"10.1016/j.reth.2026.101070","DOIUrl":"10.1016/j.reth.2026.101070","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoporosis (OP) represents a metabolic bone disorder characterized by reduced bone density and increased fracture susceptibility, primarily caused by an imbalance between bone resorption and formation. Osteogenic differentiation plays a critical role in OP, as it promotes bone formation processes. RAD51, a crucial gene encoding a protein essential for homologous recombination repair of DNA double-strand breaks, is central to maintaining genomic stability and ensuring accurate DNA repair. Previous investigations conducted by our research team have suggested the involvement of RAD51 in the pathogenesis of OP. The objective of this study was to explore the signaling pathways associated with RAD51.</div></div><div><h3>Methods</h3><div>MC3T3-E1 cells were induced to undergo osteogenic differentiation and exposed to a microgravity environment to simulate OP-like conditions. Furthermore, an ovariectomized (OVX) mouse model was established to mimic OP. Osteogenic differentiation was evaluated through Alizarin Red S staining for calcium deposition and alkaline phosphatase (ALP) staining to assess ALP activity. DNA damage was quantified using the comet assay, while protein expression profiles were analyzed via Western blot.</div></div><div><h3>Results</h3><div>Experimental results showed a significant downregulation of RAD51 expression in OP models. Notably, RAD51 overexpression promoted osteoblast differentiation and mitigated DNA damage in these models. Mechanistic studies further revealed that RAD51 suppresses activation of the cGAS-STING signaling pathway, which has been shown to negatively regulate osteoblast differentiation. In OVX mice, RAD51 overexpression mitigated bone loss, promoted osteoblast differentiation, and reduced DNA damage.</div></div><div><h3>Conclusion</h3><div>RAD51 facilitated osteogenic differentiation and attenuated DNA damage in OP by modulating the cGAS-STING signaling pathway, offering a potential novel therapeutic target for OP treatment.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101070"},"PeriodicalIF":3.5,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077068","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":"Intra-articular injections of platelet-rich plasma suppress cartilage degeneration in a mouse model of knee osteoarthritis","authors":"Yasumasa Momoi ,&nbsp;Yoshitomo Saita ,&nbsp;Ryosuke Nakajima ,&nbsp;Sayuri Uchino ,&nbsp;Hirofumi Nishio ,&nbsp;Shin Fukusato ,&nbsp;Takanori Wakayama ,&nbsp;Yohei Kobayashi ,&nbsp;Atsushi Furuhata ,&nbsp;Hiroshi Ikeda ,&nbsp;Kazuo Kaneko ,&nbsp;Muneaki Ishijima","doi":"10.1016/j.reth.2026.101072","DOIUrl":"10.1016/j.reth.2026.101072","url":null,"abstract":"<div><h3>Introduction</h3><div>Pain-relieving drugs, such as nonsteroidal anti-inflammatory drugs and hyaluronic acid, are standard treatments for knee osteoarthritis (OA); however, no disease-modifying drugs exist for knee OA. Platelet-rich plasma (PRP) is a novel treatment with both symptom improvement and disease-modifying effects; however, the underlying mechanism remains unknown. In addition, the biologically active substances contained in PRP differ greatly depending on the purification method used. This controlled laboratory study aimed to investigate the therapeutic effects of two types of PRP with different white blood cell concentrations on knee OA using an animal model.</div></div><div><h3>Methods</h3><div>Leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) were prepared from 10-week-old female C57BL/6 mice. A mouse model of knee osteoarthritis was generated by the unilateral transection of the medial meniscus in the right hind limb. Mice were randomly assigned to three treatment groups that received 6 μL intra-articular injections of either phosphate-buffered saline (control), LR-PRP, or LP-PRP at 2-, 4-, and 6-weeks post-surgery. Mice were sacrificed 12 weeks post-surgery and histologic analysis, immunohistochemistry analysis for CD68 and three‐dimensional micro-computed tomography (3DμCT) of knee joints were analyzed. Hind limb weight-bearing distribution was measured preoperatively and at 4- and 12-weeks post-surgery. Statistical analyses were performed using GraphPad Prism 9.0.2. P-values of &lt;5 % were considered statistically significant.</div></div><div><h3>Results</h3><div>Histological analysis of the femoral medial condyle (Osteoarthritis Research Society International (OARSI) score) showed that both the LP and LR groups had significantly suppressed cartilage destruction compared with the Phosphate Buffered Saline (PBS) group (P = 0.01). The percentage of CD68-positive synovial macrophages in the lateral joint was significantly lower in the LR group than in the PBS group (PBS: 2.0 ± 2.9 %, LR: 0.6 ± 1.3 %, LP: 0.9 ± 1.9 %; P = 0.02). The affected-side load rate (%) increased in the LR and LP groups, with a significant increase observed in the LR group from week four. PBS group, Pre/4w/12w = 36.0 ± 4.8/33.8 ± 6.8/36.2 ± 7.4 % (P = 0.60); LR group, Pre/4w/12w = 31.9 ± 2.2/34.3 ± 8.3/44.2 ± 4.8 % (P &lt; 0.01); LP group, Pre/4w/12w = 33.5 ± 7.4/36.1 ± 7.4/42.0 ± 5.2 % (P = 0.02). Conversely, no significant difference in BMD was observed between groups.</div></div><div><h3>Conclusions</h3><div>Intra-articular injection of LR- and LP-PRP attenuated cartilage degeneration in the medial femoral condyle in a mouse model of knee osteoarthritis.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101072"},"PeriodicalIF":3.5,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077152","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":"A thermo-responsive sol–to–gel phase transition hydrogel for sustained delivery of mesenchymal stem cell-derived exosomes","authors":"Lefeng Liu ,&nbsp;Lijuan Yang ,&nbsp;Zhiguo Xu ,&nbsp;Zhilong Dong ,&nbsp;Ze Xu ,&nbsp;Shaorong Gao ,&nbsp;Xiaoyu Liu ,&nbsp;Yong Kong","doi":"10.1016/j.reth.2026.101073","DOIUrl":"10.1016/j.reth.2026.101073","url":null,"abstract":"<div><h3>Introduction</h3><div>Mesenchymal stem cells-derived exosomes (MSC-Exo) have significant therapeutic potential in regenerative medicine but face challenges such as rapid systemic clearance and poor retention at target sites. In this study, a thermo-responsive sol–to–gel phase transition hydrogel based on sodium alginate (SA), cellulose nanofibrils (CNF) and poloxamer 407 (P407) was prepared for sustained delivery of MSC-Exo.</div></div><div><h3>Methods</h3><div>The MSC-Exo loaded CNF/SA hydrogel was prepared, which was freeze-dried and then dispersed in the P407 solution at room temperature. The mixture of CNF/SA/MSC-Exo and P407 could undergo thermo-responsive sol–to–gel phase transition due to the thermosensitive property of P407, and thus the CNF/SA/MSC-Exo was encapsulated in the P407 gel at physiological temperature (37 °C).</div></div><div><h3>Results</h3><div>Owing to the high degradation ratio of P404 gel and swelling ratio of CNF/SA hydrogel at physiological pH (∼7.4), sustained delivery of MSC-Exo from the gel was achieved with a high cumulative release of 80 % after 120 h. Cytotoxicity assay showed that the CNF/SA/P407 gel has excellent biocompatibility.</div></div><div><h3>Conclusions</h3><div>These findings provide a feasible strategy to achieve the sustained delivery of Exo for regeneration therapy, giving valuable references for future research.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101073"},"PeriodicalIF":3.5,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077071","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":"2026-01-21","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":"Monthly multiple injections of leukocyte-poor platelet-rich plasma (ACP®) for knee osteoarthritis: clinical effectiveness across KL grades, dose-response plateau at four, and 24-month durability","authors":"Masahiko Kemmochi","doi":"10.1016/j.reth.2026.101067","DOIUrl":"10.1016/j.reth.2026.101067","url":null,"abstract":"<div><h3>Background</h3><div>Monthly, ultrasound-guided intra-articular injections of leukocyte-poor platelet-rich plasma (ACP®) are widely used for knee osteoarthritis (KOA), but optimal dosing and cumulative exposure remain unclear.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed prospectively planned ACP treatments at a single clinic. Knees with KL1-4 received fixed per-knee doses (3 mL [3A] or 6 mL [6A]) monthly up to six sessions. Primary outcome was VAS pain; secondary outcomes were KOOS (Pain/ADL/QoL), OMERACT-OARSI response, MOAKS-BML, and joint effusion (JF). ANCOVA for ΔVAS at 12 months adjusted for baseline VAS and prespecified covariates; longitudinal mixed-effects models and segmented regression assessed dose-response and breakpoint.</div></div><div><h3>Results</h3><div>Pain improved at 12 months (n = 115) and was maintained at 24 months (n = 67). Segmented regression identified a dose-response plateau around the 4th injection. The 6 mL regimen showed no robust adjusted advantage over 3 mL at 12 months. KOOS domains and OMERACT-OARSI responder rates improved at 12 months and persisted at 24 months. MOAKS-BML decreased from 12 to 24 months; JF tended to decline. No serious adverse events related to ACP injections were documented.</div></div><div><h3>Conclusions</h3><div>Under a fixed monthly protocol mirroring our LR-PRP schedule, ACP (LP-PRP) produced clinically meaningful improvements across KL1-4 with a practical evaluation horizon through the 4th injection and no clear per-session volume benefit of 6 mL over 3 mL. Prospective randomization of dose within a monthly-multiple framework is warranted.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101067"},"PeriodicalIF":3.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037165","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":"Efficacy and safety of autologous adipose-derived stem cells combined with platelet-rich plasma for periodontal regeneration: a multicenter, randomized, open-label, parallel-group comparative trial","authors":"Morikuni Tobita ,&nbsp;Yosuke Masubuchi ,&nbsp;Yorimasa Ogata ,&nbsp;Akio Mitani ,&nbsp;Takeshi Kikuchi ,&nbsp;Jun-Ichiro Hayashi ,&nbsp;Taku Toriumi ,&nbsp;Anna Arita ,&nbsp;Jorge Luis Montenegro Raudales ,&nbsp;Hiroshi Mizuno ,&nbsp;Yuki Suzuki ,&nbsp;Keiko Wakana ,&nbsp;Hikari Yoneda ,&nbsp;Masahiro Kino-oka ,&nbsp;Tomohiro Morio ,&nbsp;Kiyoshi Okada ,&nbsp;Shinya Murakami ,&nbsp;Masaki Honda","doi":"10.1016/j.reth.2026.101062","DOIUrl":"10.1016/j.reth.2026.101062","url":null,"abstract":"<div><h3>Introduction</h3><div>Periodontitis is a chronic inflammatory disease caused by dental biofilm that destroys the periodontal tissues supporting the teeth. We aimed to evaluate the efficacy and safety of co-transplantation of autologous adipose-derived mesenchymal stem cells (ASCs) with platelet-rich plasma (PRP) compared to enamel matrix derivative (EMD) for regenerating periodontal tissue damaged by chronic periodontitis.</div></div><div><h3>Methods</h3><div>In this multicenter, randomized, open-label, parallel-group phase II therapeutic equivalence trial, we assessed the effects of ASCs with PRP versus EMD on alveolar bone height and width, as well as other periodontal indices. Measurements of primary and secondary endpoints and periodontal tissue indices were performed at baseline, the day of transplantation, and at 12, 24, and 36 weeks post-transplantation. Data were analyzed using Student's t-test.</div></div><div><h3>Results</h3><div>Of the 21 patients initially recruited, 9 in the ASCs + PRP group and 6 in the EMD group completed the study. The ASCs + PRP treatment demonstrated greater regenerative potential than that of EMD, with a significantly higher alveolar bone height at 36 weeks post-treatment. Patients receiving ASCs + PRP treatment showed a statistically higher mean height of new alveolar bone in the transplanted area than those in the EMD group. Clinical attachment levels improved significantly from baseline at 12, 24, and 36 weeks in the ASCs + PRP group; however, no significant difference in clinical attachment gain was observed between the two groups. Adverse events in the ASCs + PRP group were neither related to the implantation site nor to the treatment.</div></div><div><h3>Conclusions</h3><div>Co-transplantation of ASCs with PRP is a safe and effective approach for periodontal regeneration, offering a promising therapeutic strategy for the treatment of periodontitis.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101062"},"PeriodicalIF":3.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976703","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":"Immune synapse molecules knockout in induced pluripotent stem cells enables broad NK cell resistance in T cell progeny","authors":"Jing Zhang ,&nbsp;Keisuke Sumide ,&nbsp;Keitaro Kanie ,&nbsp;Akihiro Ishikawa ,&nbsp;Munehiro Yoshida ,&nbsp;Tomoko Ishii ,&nbsp;Bo Wang ,&nbsp;Shin Kaneko","doi":"10.1016/j.reth.2026.101060","DOIUrl":"10.1016/j.reth.2026.101060","url":null,"abstract":"<div><h3>Introduction</h3><div>Allogeneic iPSCs provide a potential source for regenerative T cell therapies, yet their clinical application remains limited by immune rejection driven by human leukocyte antigen (HLA) incompatibility. Knockout of β2-microglobulin (B2M) eliminates HLA class I expression and protects against CD8⁺ T cell-mediated killing, but paradoxically provokes natural killer (NK) cell activation via the “missing-self” response. Existing approaches seek to enhance inhibitory signaling or dampen activating signals, yet these approaches achieve only partial NK evasion due to the extraordinary heterogeneity of NK receptor repertoires.</div></div><div><h3>Methods</h3><div>We developed a broader and more universal immune evasion strategy by targeting immune synapse (IS) adhesion molecules that critical for NK–target cell engagement. Building on our previously reported hypoimmunogenic iPSC-derived T cell (iT cell) platform (B2M^KOCIITA^KOPVR^KO with HLA-E overexpression), we engineered double-knockout (dKO) iT cells lacking CD54 (ICAM-1) and CD58 (LFA-3) using CRISPR/Cas9-mediated gene editing. These two ligands play key roles in stabilizing NK–target immunological synapses.</div></div><div><h3>Results</h3><div>Functionally, dKO iT cells exhibited marked resistance to NK cell–mediated cytotoxicity both in vitro and in vivo in human IL-15 transgenic mouse model, while maintaining iT cell cytotoxic effector functions. By disrupting the physical interface required for NK engagement, this approach provides broad protection against diverse NK cell subsets and complements existing HLA-focused immune evasion strategies.</div></div><div><h3>Conclusions</h3><div>Our findings establish a potentially versatile platform for generating universal, NK-resistant iT cells and advance the translational potential of iPSC-based immunotherapies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101060"},"PeriodicalIF":3.5,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976704","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":"Tissue and organ engineering: Investor sentiments and analysis","authors":"Frida Velcani ,&nbsp;Erica Keyes ,&nbsp;José Luis Caraveo III ,&nbsp;James Reohr ,&nbsp;Craig D'Cruz ,&nbsp;Andrew Osterman ,&nbsp;Deirdre C. O'Donnell","doi":"10.1016/j.reth.2026.101066","DOIUrl":"10.1016/j.reth.2026.101066","url":null,"abstract":"<div><h3>Introduction</h3><div>Regenerative medicine involves restoring natural function by replacing or regenerating human cells, tissues, or organs. Despite projections of significant market growth, venture capital (VC) investment in tissue and organ engineering has recently declined.</div></div><div><h3>Methods</h3><div>We conducted a mixed-methods study using structured surveys and qualitative interviews. VC investors with experience in healthcare sectors (biotechnology, tissue engineering, and medical technology) were invited to complete a survey and participate in interviews.</div></div><div><h3>Results</h3><div>We received 22 survey responses and conducted 9 interviews (April–May 2025). Prior exposure to regenerative medicine was significantly associated with future investment likelihood (p = 0.0464). Investment potential strongly correlated with assets under management (ρ = 0.67) and investment stage (ρ = 0.66). Among 20 respondents, clinical validation (n = 8) and adoption (n = 8) were most often cited as major investment drivers, followed by reimbursement and regulatory challenges. Interviews emphasized four factors shaping VC interest in tissue and organ engineering: prior investment experience, time horizon misalignment, clinical risk expectations, and market readiness.</div></div><div><h3>Discussion</h3><div>Startups can improve appeal by targeting long-horizon investors, outlining clinical and regulatory pathways, and generating robust, comparative evidence to support value-based reimbursement.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101066"},"PeriodicalIF":3.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976705","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":"2026-01-10","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":"First-in-human study to investigate the safety and efficacy of effective-mononuclear cell therapy for radiogenic xerostomia","authors":"Takashi I ,&nbsp;Mayumi Iwatake ,&nbsp;Takako Yoshida ,&nbsp;Kazuhiro Nagai ,&nbsp;Yuka Hotokezaka ,&nbsp;Mika Nishihara ,&nbsp;Ryo Honma ,&nbsp;Hiroshi Harada ,&nbsp;Munehiro Hayashida ,&nbsp;Toshiki Nagano ,&nbsp;Riho Kanai ,&nbsp;Seigo Ohba ,&nbsp;Atsutoshi Yoshimura ,&nbsp;Haruchika Masuda ,&nbsp;Takayuki Asahara ,&nbsp;Yasushi Miyazaki ,&nbsp;Atsushi Kawakami ,&nbsp;Izumi Asahina ,&nbsp;Makoto Seki ,&nbsp;Yoshinori Sumita","doi":"10.1016/j.reth.2025.101059","DOIUrl":"10.1016/j.reth.2025.101059","url":null,"abstract":"<div><h3>Background</h3><div>Salivary gland (SG) hypofunction is the most common complication following radiotherapy for head and neck cancer. Currently, there are no effective therapies for radiation-induced xerostomia. We recently developed a novel therapy for preclinical studies using effective-mononuclear cells (E-MNCs) induced from autologous peripheral blood mononuclear cells (PB-MNCs) via a new primary culture system for treatment of radiation-induced xerostomia. However, the safety and effectiveness of E-MNC therapy have not been assessed in humans. The objective of this first-in-human study was to evaluate the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia.</div></div><div><h3>Methods</h3><div>This first-in-human study was an open-label, single-center, two-step dose escalation study. A total of 5 patients who had no recurrence of head and neck cancer over a 5-year period following radiation therapy and suffered from radiation-induced xerostomia received a transplantation of E-MNCs to one-sided submandibular gland (SMG). The primary endpoint was the safety of the protocol. The secondary endpoint was effectiveness evaluated based on change from baseline in whole-saliva secretion, MRI/CT-evaluated volume of the SMG and subjective/objective symptoms after intervention. The duration of the intervention was 1 year.</div></div><div><h3>Results</h3><div>During follow-up, no treatment-related adverse events were detected. The stimulated whole salivary flow rate increased from an average of 3.86 mL/10 min at baseline to 5.16 mL/10 min at 6 months post–investigational intervention. Additionally, subjective/objective symptoms improved in 4 of 5 treated patients. By contrast, imaging findings revealed no obvious changes in MRI/CT-evaluated volume of SMGs due to conspicuous progression of atrophy and fibrosis compared with baseline.</div></div><div><h3>Conclusion</h3><div>This is the first clinical study to evaluate the safety and efficacy of E-MNC treatment in patients with severe radiation-induced xerostomia. The results of our study indicate that E-MNC treatment is safe and effective, and provide valuable information that will aid in designing subsequent clinical studies.</div></div><div><h3>Trial registration</h3><div>This study was registered with the Japan Registry of Clinical Trials (<span><span>http://jrct.niph.go.jp</span><svg><path></path></svg></span>) as jRCTb070190057.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101059"},"PeriodicalIF":3.5,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924579","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}