Regenerative Therapy最新文献

{"title":"Qianzheng powder promotes facial nerve regeneration via BDNF/TrkB/CREB pathway activation","authors":"Liang Chen,&nbsp;Chaoqun Wang,&nbsp;Lixin Jiang,&nbsp;Qiang Xie,&nbsp;Hongru Qin,&nbsp;Ziheng Zhang","doi":"10.1016/j.reth.2025.101048","DOIUrl":"10.1016/j.reth.2025.101048","url":null,"abstract":"<div><h3>Introduction</h3><div>Facial nerve injury (FNI) is a common peripheral neuropathy that severely impairs facial function and quality of life. Qianzheng Powder (QZP) is a traditional Chinese herbal formula used to treat facial paralysis clinically, yet its neuroprotective mechanisms remain unclear. This study aims to evaluate the therapeutic effects of QZP on FNI and potential underlying mechanisms.</div></div><div><h3>Methods</h3><div>A FNI model was established in male C57BL/6 mice by performing facial nerve crush surgery. QZP (3.51 g/kg) was administered orally once daily for 14 days post-surgery. Facial function was assessed behaviorally. Tissue samples were collected on day 21 for histological evaluation, qPCR and Western blotting. Liver and kidney safety were also assessed via H&amp;E staining and serum biochemical markers.</div></div><div><h3>Results</h3><div>QZP significantly improved facial motor function from day 7 post-injury. Additionally, QZP treatment mitigated neuronal loss in the facial motor nucleus, attenuated buccinator muscle atrophy, and enhanced myelin regeneration, as evidenced by increased MPZ and MBP expression. These were consistent with the increace of the BDNF, TrkB, and <em>p</em>-CREB/CREB expressions in QZP-treated mice. No hepatic or renal toxicity was detected.</div></div><div><h3>Conclusion</h3><div>QZP promotes structural and functional recovery of facial nerve following injury, likely through activation of the BDNF/TrkB/CREB axis, and demonstrates a favorable safety profile. These findings support its potential as a therapeutic adjunct in peripheral nerve repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101048"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691062","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 favorable role of recombinant collagen peptide in periosteal cell-derived osteoregeneration","authors":"Tran Thi Thuy Diep ,&nbsp;Naoki Takahashi ,&nbsp;Takahiro Tsuzuno ,&nbsp;Shunya Motosugi ,&nbsp;Yuta Ueda ,&nbsp;Aoi Yamada ,&nbsp;Yukari Aoki-Nonaka ,&nbsp;Masaki Nagata ,&nbsp;Koichi Tabeta","doi":"10.1016/j.reth.2026.101064","DOIUrl":"10.1016/j.reth.2026.101064","url":null,"abstract":"<div><h3>Background</h3><div>Human periosteal cells (hPCs) possess high osteogenic potential and are considered promising candidates for regenerative therapy. Recombinant human collagen peptide (RCP), a xeno-free biomaterial enriched with arginine-glycine-aspartic acid (RGD) sequences, provides a stable and biocompatible scaffold that may enhance cellular functions.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate the biocompatibility of RCP with hPCs and its effects on osteogenic functions <em>in vitro</em> and in <em>vivo</em>.</div></div><div><h3>Materials and methods</h3><div>Cell viability was assessed by MTT assay at various RCP concentrations. Cell adhesion and migration were examined using fluorescence-based adhesion and Oris™ migration assays. Gene expression profiles were analyzed by RNA-sequencing and quantitative PCR. Alkaline phosphatase assay (ALP) and Alizarin Red staining (ARS) were performed to evaluate osteogenic differentiation. For <em>in vivo</em> analysis, a rat calvarial critical-size defect model was used to evaluate bone regeneration following transplantation of hPCs with or without RCP.</div></div><div><h3>Results</h3><div>RCP exhibited no cytotoxic effects and enhanced the adhesion and migration of hPCs. RNA-seq and qPCR analyses revealed upregulation of extracellular matrix- and osteogenesis-related genes, including COL1A1, SERPINH1, ALP, RUNX2, and OCN. Moreover, RCP enhanced osteogenic differentiation, as demonstrated by increased ALP activity and greater calcium deposition in ARS. <em>In vivo</em>, micro-CT analysis showed no significant difference in new bone volume among groups, whereas immunohistochemical analysis revealed increased numbers of OCN- and BMP-2-positive cells in RCP-treated defects, indicating enhanced osteogenic activity.</div></div><div><h3>Conclusion</h3><div>RCP supports the osteogenic potential of hPCs by promoting adhesion, migration, and osteogenesis-related gene expression, and enhancing osteogenic activity <em>in vitro</em> and <em>in vivo</em>. These findings suggest that RCP is a promising biomaterial for periosteal cell-based regenerative therapies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101064"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924573","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":"In vitro polarized macrophages ameliorate adverse cardiac remodeling in a mouse model of transverse aortic constriction","authors":"Ulugbek Yakhshimurodov ,&nbsp;Kizuku Yamashita ,&nbsp;Takuji Kawamura ,&nbsp;Kenji Miki ,&nbsp;Takura Taguchi ,&nbsp;Shunsuke Saito ,&nbsp;Imad Abugessaisa ,&nbsp;Shigeru Miyagawa","doi":"10.1016/j.reth.2026.101061","DOIUrl":"10.1016/j.reth.2026.101061","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Heart failure (HF) caused by pressure overload remains as one of the leading causes of morbidity and mortality worldwide, which can manifest itself in a wide range of clinical scenarios. Current therapeutic strategies are limited to lifestyle changes, pharmacological measures, and devices aimed at supporting heart function. This poses a challenge in the search for new strategies for disease management. Macrophages, constituting nearly 10 % of non-myocyte cells in a healthy heart are considered a means to fill this gap due to their pleiotropic phenotype, which extends beyond the well-known functions of phagocytosis and antigen presentation. In this study, we evaluated the efficacy of bone marrow mononuclear cell (BMNC)-derived macrophages (BMNC-Mφ) in treating a mouse model of transverse aortic constriction (TAC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In &lt;em&gt;in vitro&lt;/em&gt; experiments, BMNC were polarized into BMNC-Mφ using a previously established protocol. We then performed transcriptomic analysis to confirm BMNC-Mφ marker genes compared to BMNC. BMNC-Mφ phenotypes were further validated by flow cytometry and RT-qPCR. In &lt;em&gt;in vivo&lt;/em&gt; experiments, all mice underwent TAC surgery (day 0). On days 7 and 14 post-TAC, mice in the experimental and control groups received intravenous injections of approximately 3 × 10&lt;sup&gt;6&lt;/sup&gt; BMNC-Mφ or PBS, respectively. Heart function was assessed weekly by transthoracic echocardiography at baseline and 7, 14, 21, and 28 days post-TAC. Additionally, we monitored &lt;em&gt;in vivo&lt;/em&gt; transcriptome dynamics over time using time-resolved deep RNA sequencing profiles of heart tissues from healthy, 1 day post-TAC, 8 days post-TAC, and 16 days post-TAC mice. Time-course transcriptomic profiling was followed by histological analysis of excised hearts on day 28.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;BMNC-Mφ showed phenotype similar to that of resident cardiac macrophages, with increased expression of key anti-inflammatory macrophage markers, including &lt;em&gt;Igf1, Arg1, Retnla, Ang2, Anxa2,&lt;/em&gt; and others. &lt;em&gt;In vivo&lt;/em&gt; application of BMNC-Mφ further confirmed their potential to mitigate adverse cardiac remodeling in TAC model. Mice receiving BMNC-Mφ better tolerated mechanical stress, as reflected in preserved LV function (LVEF [52.3 % vs. 45.6 %, p = 0.0152], LVFS [22.6 % vs. 19.2 %, p = 0.0208], and LVIDs [2.65 mm vs. 3.2 mm, p = 0.0261]), as well as structure (fibrosis area [5.6 % vs. 10.67 %, p &lt; 0.01]). In addition, BMNC-Mφ promoted angiogenesis (2120.4 ± 25.5 per mm&lt;sup&gt;2&lt;/sup&gt; vs. 1512.4 ± 34 per mm&lt;sup&gt;2&lt;/sup&gt;, p &lt; 0.05) and controlled cardiomyocyte growth, which was seen in the smaller short-axis diameter of cardiomyocytes in BMNC-Mφ-treated group (17.2 ± 0.18 μm vs. 19.45 ± 0.46 μm, p &lt; 0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The main conclusion drawn from our results is that BMNC-Mφ improved or at least preserved LV function and architecture through metabolic recove","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101061"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924578","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":"Smart integrated biomaterial systems for precision and optimized delivery of MSCs and their exosomes: Transforming wound healing and organ regeneration","authors":"Fatemeh Rafati ,&nbsp;Zeynab Ghorbani ,&nbsp;Tahereh Manoochehrabadi ,&nbsp;Farbod Khosravi ,&nbsp;Jila Majidi ,&nbsp;Fatemeh Eskandari ,&nbsp;Mohamad Eftekhary ,&nbsp;Hajar Nasiri","doi":"10.1016/j.reth.2025.101045","DOIUrl":"10.1016/j.reth.2025.101045","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) and their exosome (MSCs-Exos) have been shown to be major therapeutic candidates in regenerative medicine due to their inherent capacity for modulating immune response, promoting angiogenesis, and repairing tissues. However, clinical application of MSCs and MSCs-Exos is hindered by various intrinsic barriers, such as poor survival of transplanted MSCs, quick systemic clearance of exosomes, uncontrolled release of therapeutic payloads, and loss of function in severe pathological situations, such as chronic wounds and fibrotic tissues. To overcome these limitations, recent advances have focused on the design of modern delivery systems to enhance the stability, bioavailability, and functionality of MSCs and MSCs-Exos. These platforms include responsive hydrogels, engineered nanoparticles, and multi responsive intelligent dressings that mirror protective microenvironments in general and provide controlled, long-term distribution of bioactive elements. This current review focuses on such innovative approaches that enhance regeneration results in strong preclinical models, maximize therapeutic delivery, and boost MSCs and exosome survival. Despite remarkable advancements, major obstacles still exist, such as guaranteeing biosafety, achieving scale production, and obtaining regulatory approvals. The combination of MSCs and MSCs-Exos therapies with intelligent, responsive biomaterials capable of providing antimicrobial function and active monitoring has the potential to revolutionize tissue regeneration and wound healing and make MSCs and MSCs-Exos invaluable resources in precision regenerative medicine of the future.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101045"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622029","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":"Innovative synergy of bone xenograft and quercetin in the alveolar bone socket: Histological and immunohistochemical assessment of healing","authors":"Christian Khoswanto ,&nbsp;Ira Kusuma Dewi","doi":"10.1016/j.reth.2026.101076","DOIUrl":"10.1016/j.reth.2026.101076","url":null,"abstract":"<div><h3>Background</h3><div>After an extraction, the alveolar bone may undergo shrinkage, making it more challenging to place dental implants and compromising the appearance of prosthetic rehabilitation. Studies show that alveolar bone resorption could reach 50% of the original ridge width within the first six months after extraction. Xenografts have shown promising outcomes because they are biocompatible, resemble human bone, and facilitate the growth of new bone. Xenografts, on the other hand, are mostly used as a scaffold for new bone to grow on and don't cause bone growth on their own. Because of this, their integration and remodeling often take a long time and don't always happen completely. This has led researchers to look into other biological agents that can speed up healing and bone growth. Quercetin has been shown to be bioactive, meaning it can fight inflammation and act as an antioxidant. Using a bone xenograft or another suitable carrier or scaffold with quercetin may make it more stable and concentrated at the defect site. This combination may provide the osteoconductive framework necessary for new bone deposition, as well as the osteopromotive qualities of quercetin, to accelerate the cellular and molecular processes related to healing.</div></div><div><h3>Methods</h3><div>This study involved 64 healthy Wistar rats. The animals were randomly divided into four groups. The animals were euthanized seven to twenty-one days after extraction.</div><div>Combining quercetin with a xenogenic bone graft greatly speeds up the repair of the alveolar socket. The combination encourages the production of new bone early on.</div></div><div><h3>Conclusion</h3><div>The combination of quercetin and bone xenograft significantly improved the repair of alveolar bone sockets in Wistar rats.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101076"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187795","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":"Low-dose lipopolysaccharide pretreatment enhanced the proliferation and antibacterial activity of human adipose-derived mesenchymal stem cells","authors":"Linling Li ,&nbsp;Jielin Diao ,&nbsp;Feng Wang ,&nbsp;Xia Wang ,&nbsp;Yicai Liu ,&nbsp;Xiaoming Fu","doi":"10.1016/j.reth.2025.101057","DOIUrl":"10.1016/j.reth.2025.101057","url":null,"abstract":"<div><h3>Introduction</h3><div>Adipose-derived mesenchymal stem cells (ADSCs) have been widely investigated for their pro-angiogenic and immunomodulatory roles in the repair of infected wounds. However, the direct antimicrobial effects of ADSCs and the underlying regulatory mechanisms remain poorly characterized. In particular, the functional modulation of ADSCs by low-dose lipopolysaccharide (LPS) preconditioning has not been systematically investigated.</div></div><div><h3>Methods</h3><div>We evaluated the effects of LPS preconditioning on the proliferation and apoptosis of human ADSCs (hADSCs), as well as the antimicrobial activity and wound-healing potential of hADSC-conditioned medium (hADSC-CM).</div></div><div><h3>Results</h3><div>Analysis demonstrated that at concentrations ranging from 10 to 500 ng/mL, LPS significantly enhanced the proliferation of hADSCs, with the highest viability observed at 500 ng/mL and no evidence of increased apoptosis. Moreover, LPS preconditioning markedly upregulated the expression of antimicrobial peptides (LL-37 and HBD-2) in hADSC-CM, leading to improved inhibition of <em>Staphylococcus aureus</em> and <em>Escherichia coli</em> growth. In vivo experiments further confirmed that 500 ng/mL of LPS-hADSC-CM significantly accelerated the healing of infected wounds, increased collagen deposition, and downregulated the expression of iNOS, thus suggesting enhanced inflammation resolution and tissue regeneration.</div></div><div><h3>Conclusion</h3><div>These findings highlight the capacity of LPS preconditioning to potentiate the biological functions of hADSCs, enhancing the antimicrobial and regenerative efficacy of hADSC-CM, and providing a promising strategy for the treatment of chronically infected wounds.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101057"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839203","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":"Microbial contamination risks and clinical safety in platelet-rich plasma therapy and evaluation of rapid microbial detection methods","authors":"Anna Arita ,&nbsp;Yoshitomo Saita ,&nbsp;Naho Fujiwara ,&nbsp;Yasuhiro Homma ,&nbsp;Morikuni Tobita","doi":"10.1016/j.reth.2025.11.008","DOIUrl":"10.1016/j.reth.2025.11.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Platelet-rich plasma (PRP) is widely used for pain relief, wound healing, and so on. However, recent reports have documented cases of infections occurring after PRP therapy. In this study, we aimed to examine potential microbial contamination risks associated with PRP therapy and evaluate rapid microbial detection methods suitable for clinical use.</div></div><div><h3>Methods</h3><div>We assessed the risk of microbial contamination during blood collection, PRP preparation, and sterility testing. To evaluate suitable detection methods, we compared the microbial detection sensitivities of flow cytometry (FCM) and polymerase chain reaction (PCR) for identifying microbial contamination in PRP. For this purpose, PRP samples were inoculated with <em>Staphylococcus aureus</em>, <em>Streptococcus</em> spp., <em>Cutibacterium acnes</em>, <em>Micrococcus</em> spp., <em>Bacillus subtilis</em>, and <em>Candida albicans</em>.</div></div><div><h3>Results</h3><div>Following skin disinfection, microbial colonies were detected at the venipuncture site in six out of ten patients. Environmental monitoring identified airborne microbial colonies in two out of three anonymous PRP preparation facilities. Sterility tests revealed negative results for all 85 residual PRP and 15 platelet-poor plasma (PPP) cases. FCM sensitivity for microbial detection in PRP was effective at a concentration of 10²–10³ colony forming units (cfu)/mL or higher. While <em>C. albicans</em> could not be detected separately from non-specific PRP signals using FCM, it was detectable in PPP at ≥10² cfu/mL. PCR sensitivity for microbial detection was excellent when analyzing pure microbial suspensions, however, it yielded a high rate of false-negative and false-positive results when PRP samples contained certain microbial strains.</div></div><div><h3>Conclusion</h3><div>The risks of microbial contamination were identified during both venipuncture and PRP production. To reduce these risks, it may be necessary to improve disinfection protocols for venipuncture sites and blood collection methods, implementing appropriate facility-specific measures. Although requiring further detection sensitivity improvements, FCM is a promising method for detecting viable bacteria in PRP. Given that microbial contamination cannot be completely eliminated, clinicians providing PRP therapy should remain alert to the potential for postoperative infections and ensure appropriate follow-up protocols are established.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101043"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532468","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":"Leukocyte-rich versus leukocyte-poor platelet-rich plasma for Osteoarthritis: A systematic review","authors":"Marta Martín-Vega ,&nbsp;Álvaro Gómez-Carrión ,&nbsp;Ignacio Zaragoza-García ,&nbsp;Ismael Ortuño-Soriano ,&nbsp;Arian Marcelino-Argemi ,&nbsp;Paola Sanz-Wozniak ,&nbsp;Rebeca Saludes-Llamas ,&nbsp;Rubén Sánchez-Gómez","doi":"10.1016/j.reth.2026.101078","DOIUrl":"10.1016/j.reth.2026.101078","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoarthritis is an increasingly prevalent condition with limited conservative treatments. Platelet-rich plasma (PRP) therapy has gained attention, but its efficacy may depend on the type used. In particular, leukocyte-rich (LR-PRP) and leukocyte-poor (LP-PRP) formulations may influence outcomes, yet direct comparisons are limited.</div></div><div><h3>Methodology</h3><div>a systematic literature search and analysis of clinical trials, through PubMed database, were conducted to evaluate the effect of leukocyte – rich and leukocyte – poor platelet rich plasma in the treatment of osteoarthritis.</div></div><div><h3>Results</h3><div>11 articles were analyzed individually, including both in vivo and <em>in vitro</em> studies, to examine the effect of leukocytes in PRP.</div></div><div><h3>Conclusion</h3><div>This review highlights that current evidence is insufficient to determine whether adding leukocytes to PRP provides a clinical benefit in the treatment of osteoarthritis. Overall, results generally show no significant differences between LR-PRP and LP-PRP, suggesting that both may be effective. Although leukocytes were initially thought to induce inflammation, there is no conclusive evidence that local reactions are directly caused by them. Given the limitations of existing studies, further research is required to clarify the role of leukocytes in PRP therapy.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101078"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147356081","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":"Anti-inflammatory and immunomodulatory effects of human induced pluripotent stem cells-derived mesenchymal stem/stromal cells and their extracellular vesicles","authors":"Yusaku Komoike ,&nbsp;Daisuke Kamiya ,&nbsp;Haruka Sasaki-Ban ,&nbsp;Atsushi Matsuda ,&nbsp;Hirokazu Matsumoto ,&nbsp;Makoto Ikeya","doi":"10.1016/j.reth.2026.101081","DOIUrl":"10.1016/j.reth.2026.101081","url":null,"abstract":"<div><h3>Introduction</h3><div>Mesenchymal stem/stromal cells (MSCs) are multipotent cells that secrete multiple factors for tissue regeneration. These tissue-derived MSCs can self-renew, but their numbers are limited and decrease with age. The previously established xeno-free MSCs (XF-iMSCs), derived from human induced pluripotent stem cells (hiPSCs) of the neural crest cell (NCC) lineage, can regenerate damaged bone and skeletal muscle. However, the anti-inflammatory and immunomodulatory effects of XF-iMSCs have not been elucidated. Here, we aimed to elucidate the effects of XF-iMSCs and their extracellular vesicles (XF-iEv) on inflammation and immunomodulation.</div></div><div><h3>Methods</h3><div>XF-iMSCs were generated from hiPSCs using NCCs. Mouse PBMCs and splenocytes were obtained from male C57BL/6 mice. The MSCs were characterized using flow cytometry. Cytokine secretion stimulated by lipopolysaccharides (LPS) or Dynabeads CD3/CD28 was measured by ELISA. The proliferation of CellTrace Violet-labeled effector T cells (Teff) cultured with MSCs or their EVs was analyzed using a suppression assay. EVs were purified from the MSC culture medium using a MagCapture Exosome Isolation Kit. Proteome analysis of the EVs was performed using non-labeled liquid chromatography-tandem mass spectrometry.</div></div><div><h3>Results</h3><div>XF-iMSCs expressed representative MSC cell surface markers, including CD44, CD73, and CD105, but not CD45 or HLA-DR. XF-iMSCs and human adipocyte-derived MSCs (hAC-MSCs) suppressed LPS-stimulated IL-6 and TNF-α secretion in mouse PBMCs. Suppression of LPS-induced IL-6 and TNF-α secretion by XF-iEv and hAC-MSCs (hAC-Ev) was concentration-dependent. Fifty times-concentrated EVs from both XF-iMSCs and hAC-MSCs strongly suppressed IL-2, IFN-γ, and IL-17 secretion induced by dynabeads CD3/CD28 in mouse splenocytes. The effect of XF-iMSCs against inflammatory and anti-inflammatory cytokine production induced by LPS in hPBMCs was comparable to that of primary human adipocytes, bone marrow, and umbilical cord-derived MSCs. XF-iEv (x50) strongly inhibited TNF-α secretion from LPS-stimulated human PBMCs, although there was no effect on IL-6 secretion. Condition medium (CM) from XF-iMSCs promoted IL-10 secretion but not concentrated XF-iEv (x50). XF-iMSCs suppressed Teff proliferation to a level comparable to that of hAC-MSCs. XF-iEv had 1217 proteins with unique components compared to hAC-Ev.</div></div><div><h3>Conclusions</h3><div>XF-iMSCs and their EVs exert anti-inflammatory and immunomodulatory effects in human and mouse cell-based assays and have promising therapeutic applications for autoimmune diseases.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101081"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147356071","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":"NSUN2-engineered human umbilical cord mesenchymal stem cell-derived exosomes ameliorate tendon injury by promoting DNM2 expression","authors":"Yuxin Liu ,&nbsp;Yalu Pu ,&nbsp;Qi Li ,&nbsp;Liang Yu ,&nbsp;Hailong Kou ,&nbsp;Yang Liu ,&nbsp;Zhizhong Shen ,&nbsp;Yilei Zhao","doi":"10.1016/j.reth.2025.101050","DOIUrl":"10.1016/j.reth.2025.101050","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Tendon injuries are a common musculoskeletal problem, often leading to chronic pain and disability. Current treatment options, including surgical interventions and physical therapy, have limitations in terms of efficacy and potential complications. Human umbilical cord mesenchymal stem cells (HUCMSCs) are a promising source of mesenchymal stem cells (MSCs), and exosomes derived from HUCMSCs have been shown to mediate various biological processes. This study aims to investigate the role of HUCMSC-derived exosomes in tendon injuries and the underlying mechanism.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Exosomes were isolated from HUCMSCs using differential centrifugation. Cell viability was assessed using a cell counting kit-8 assay. Cell proliferation was measured by a 5-Ethynyl-2′-deoxyuridine assay. Transwell invasion assays were conducted to analyze cell invasion, and wound-healing assays were used to evaluate cell migration. Quantitative real-time PCR (qRT-PCR) was employed to analyze DNM2 mRNA expression. Western blotting was used to detect the protein expression of NOP2/Sun RNA methyltransferase 2 (NSUN2), C cluster of differentiation 63 (CD63), CD81, and dynamin 2 (DNM2). m5C methylated RNA immunoprecipitation and RNA immunoprecipitation (RIP) assays were performed to analyze the association of NSUN2 with DNM2. Additionally, an RIP assay was conducted to study the interaction among Y-box binding protein 1 (YBX1), NSUN2, and DNM2 in injured tenocytes. Rats were subjected to superficial tendon excision and partial transection of the deep Achilles tendon to induce tendon injury. Hematoxylin and eosin (HE) staining was used to analyze the pathological conditions of Achilles tendon tissues, and an immunohistochemistry (IHC) assay was performed to detect the positive expression rates of NSUN2 protein.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;HUCMSC-derived exosomes significantly promoted the proliferation, migration, and invasion of injured tenocytes. Overexpression of NSUN2 also enhanced the proliferative, migratory and invasive abilities of injured tenocytes. The exosomes derived from NSUN2-overexpressing HUCMSCs showed a more pronounced promoting effect on injured tenocyte proliferation, migration, and invasion compared to control exosomes. NSUN2 stabilized DNM2 mRNA expression through m5C methylation modification. YBX1 interacted with NSUN2 to stabilize DNM2 expression. In addition, knockdown of DNM2 attenuated the promoting effects of HUCMSC-derived exosomes with NSUN2 overexpression on the proliferation, migration, and invasion of injured tenocytes. Moreover, exosomes derived from NSUN2-overexpressing HUCMSCs improved tendon injury in a rat model, as indicated by enhanced pathological conditions within the tendon tissues.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;HUCMSC-derived exosomal NSUN2 played a crucial role in ameliorating tendon injury by promoting DNM2 expression. The findings suggest that exosomes from NSUN2-ove","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101050"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796776","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}