Regenerative Therapy最新文献

{"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":"2026-01-09","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":"2026-01-09","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":"Low-frequency electromagnetic fields ameliorate testosterone-induced androgenetic alopecia in mice through LncRNA H19/miR-214-5p/β-catenin signal pathway","authors":"Jiang-Hua Cheng ,&nbsp;Chong-You ,&nbsp;Ting Hu ,&nbsp;Wei-Jun Fang ,&nbsp;Xiao-Min Niu ,&nbsp;Ke-Tao Du","doi":"10.1016/j.reth.2026.101069","DOIUrl":"10.1016/j.reth.2026.101069","url":null,"abstract":"<div><h3>Background</h3><div>In androgenetic alopecia (AGA), the depletion or long-term inactivity of the hair follicle stem cells (HFSCs) pool is a fundamental cause. Reviving inactive HFSCs is regarded as a promising treatment method for hair loss.</div></div><div><h3>Objective</h3><div>This study explored whether applying low-frequency electromagnetic fields (LFEMF) (1 Hz and 50 Hz) externally can enhance the activation and proliferation of HFSCs and alleviate symptoms of AGA in mice via the LncRNA H19/miR-214-5p/β-catenin signal pathway.</div></div><div><h3>Methods</h3><div>Scalp samples were obtained from 30 AGA patients and 30 healthy controls. The levels of LncRNA H19, miR-214-5p and β-catenin were assessed using qRT-PCR and Western blotting. Male C57BL/6 mice were employed to generate a dihydrotestosterone (DHT)-induced AGA model, while HFSCs were served to construct a DHT-induced in vitro cellular model. Subsequently, the effects and underlying mechanisms of LFEMFs treatment were examined through immunohistochemistry, direct observation of hair growth, cell proliferation assays, cell cycle and apoptosis analysis, as well as qRT-PCR and Western blotting. The relationship between LncRNA H19, miR-214-5p and β-catenin were further explored using RNA pull-down, RNA-binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and luciferase reporter assay.</div></div><div><h3>Results</h3><div>LFEMF stimulated hair regeneration in mice and reversed DHT-induced cell apoptosis by activating LncRNA H19/miR-214-5p/β-catenin signaling pathway.</div></div><div><h3>Conclusion</h3><div>LFEMF alleviates DHT-induced AGA and stimulates hair regrowth in mice by activating Wnt/β-catenin signaling pathway, suggesting its potential as a therapeutic strategy for AGA.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101069"},"PeriodicalIF":3.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924572","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":"Extracellular vesicles derived from adipose-derived mesenchymal stem/stromal cells prevent synovial inflammation and attenuate cartilage degeneration in rodent osteoarthritis","authors":"Yushi Maruiwa ,&nbsp;Yasuo Niki ,&nbsp;Yo Mabuchi ,&nbsp;Osamu Takeuchi ,&nbsp;Satoshi Kuronuma ,&nbsp;Yoshitsugu Fukuda ,&nbsp;Atsuhiro Fujie ,&nbsp;Akihito Oya ,&nbsp;Shu Kobayashi ,&nbsp;Masaya Nakamura","doi":"10.1016/j.reth.2025.101056","DOIUrl":"10.1016/j.reth.2025.101056","url":null,"abstract":"<div><h3>Objective</h3><div>Osteoarthritis (OA) is the most common joint disease in the elderly and a major cause of pain and disability. Recent advances in OA therapy have led to a greater variety of treatment options. Extracellular vesicles (EVs) have recently emerged as a potential therapeutic approach for OA. This study aimed to demonstrate the disease-modifying effects of adipose-derived mesenchymal stem cell-derived EVs (MSC-EVs) on OA.</div></div><div><h3>Methods</h3><div>The anti-inflammatory effects of MSC-EVs were evaluated using RAW264.7 macrophage-like cells stimulated with lipopolysaccharide and human synovial cells stimulated with IL-1β. In vivo, MSC-EVs were administered intra-articularly into knees of rats with monosodium iodoacetate (MIA)-induced OA. Pain thresholds, gait parameters, histological scores, and cytokine levels were assessed. Single-cell RNA sequencing (scRNA-seq) was performed on joint tissues to evaluate cell-specific gene expression and macrophage polarization.</div></div><div><h3>Results</h3><div>In vitro, MSC-EVs reduced the mRNA expression of IL-1β and IL-6 in RAW264.7 cells, and significantly suppressed multiple inflammatory cytokines while upregulating FGF-18 in synovial cells. In vivo, intra-articular MSC-EV injection increased pain threshold, improved gait, and reduced synovial inflammation and cartilage degeneration. scRNA-seq revealed decreased inflammatory cytokines, increased PRG4 and FGF-18 expression, and a shift in macrophage polarization toward an M2 phenotype in the EV-treated group.</div></div><div><h3>Conclusion</h3><div>MSC-EVs exert anti-inflammatory and cartilage-protective effects in OA through immune modulation and regenerative signaling, indicating their significant therapeutic potential as a disease-modifying strategy for OA.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101056"},"PeriodicalIF":3.5,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883644","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":"Mesenchymal stromal cell–derived extracellular vesicles in regenerative medicine: Standardisation, bioengineering and clinical translation","authors":"Yusuke Shimizu ,&nbsp;Yoshikazu Inoue ,&nbsp;Naoki Matsuura ,&nbsp;Tatsuya Ishii ,&nbsp;Yoshihiro Sowa ,&nbsp;Hiroshi Sunami ,&nbsp;Edward Hosea Ntege","doi":"10.1016/j.reth.2025.101058","DOIUrl":"10.1016/j.reth.2025.101058","url":null,"abstract":"<div><div>Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as promising cell-free therapeutics that recapitulate key paracrine functions of MSCs whilst mitigating limitations of viable-cell therapies. Clinical translation is hindered by inconsistent dose metrics, lack of validated potency assays, and manufacturing complexities. Here we review advances in MSC-EV standardisation, source and culture determinants, engineering and delivery platforms, and clinical applications, exemplified by chronic wound healing. We operationalise dual-metric dosing (particles <em>plus</em> protein) linked to mechanism-aligned potency assays, adopt a route-aware exposure–response framework to guide delivery strategies, and propose decision matrices aligning MSC sources and bioprocesses with indication-specific tasks. Good Laboratory Practice safety panels and Good Manufacturing Practice scale-up strategies are outlined to support regulatory readiness. Early clinical studies demonstrate feasibility and short-term safety but reveal heterogeneous efficacy, underscoring the need for harmonised dosing and potency measures. Collectively, these insights provide a roadmap to advance MSC-EVs as indication-matched regenerative medicines.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101058"},"PeriodicalIF":3.5,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839201","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":"2025-12-22","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":"Best evidence summary for platelet-rich plasma treatment of chronic wounds","authors":"Xinru Zhang ,&nbsp;Xingxing Zhang ,&nbsp;Luxin Wang ,&nbsp;Li Zhen ,&nbsp;Meiyan Lin ,&nbsp;Yanan Li ,&nbsp;Lihong Gong ,&nbsp;Haiting Zeng ,&nbsp;Weiqing Ruan ,&nbsp;Mulan Zhu","doi":"10.1016/j.reth.2025.101053","DOIUrl":"10.1016/j.reth.2025.101053","url":null,"abstract":"<div><h3>Objective</h3><div>To summarize the best evidence for platelet-rich plasma therapy in chronic wounds, providing an evidence-based foundation for standardizing its clinical practice.</div></div><div><h3>Methods</h3><div>Guided by the “6S” evidence pyramid model, we systematically searched 12 databases including Cochrane Library and Pubmed, 9 guideline websites including Guidelines International Network (GIN) and National Institute for Health and Clinical Excellence (NICE), and 10 professional websites including World Union of Wound Healing Societies (WUWHS), for relevant evidence from the establishment of the database to May 1, 2025. Two researchers independently conducted quality assessment, evidence extraction, and integration of the included literature.</div></div><div><h3>Results</h3><div>A total of 17 articles were included, comprising 3 guidelines, 5 expert consensus statements, and 9 systematic reviews. The evidence was categorized into six key treatment domains: application principles, indications and contraindications, pre-treatment preparations, treatment protocols, efficacy monitoring, and management strategies. 27 individual recommendations were derived from these categories.</div></div><div><h3>Conclusion</h3><div>Platelet-rich plasma therapy can be used as an adjunctive treatment for the management of chronic wounds. Clinicians and wound care specialists should thoroughly assess the applicability and timing of platelet-rich plasma, considering the specific clinical context, and combine it with the patient's physical condition and preferences for clinical application, promoting chronic wound healing and reducing the global disease burden of chronic wounds.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101053"},"PeriodicalIF":3.5,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839202","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":"Effect of local administration of microRNA-31/210 on bone regeneration surrounding hydroxyapatite/tricalcium phosphate -coated titanium implant in an ovariectomized rat model","authors":"Shinichi Ueki ,&nbsp;Takeshi Shoji ,&nbsp;Hideki Saka ,&nbsp;Hiroki Kaneta ,&nbsp;Hiroyuki Morita ,&nbsp;Yosuke Kozuma ,&nbsp;Nobuo Adachi","doi":"10.1016/j.reth.2025.101055","DOIUrl":"10.1016/j.reth.2025.101055","url":null,"abstract":"<div><h3>Background</h3><div>With the aging population, the prevalence of total joint arthroplasty in older adults with compromised bone conditions, such as osteoporosis, is increasing, raising concerns on the initial fixation of implants and aseptic loosening. Recent studies have highlighted the potential of microRNAs (miRNAs) to enhance osteogenesis and angiogenesis, potentially improving implant osseointegration. This study aimed to identify miRNAs with the highest osteogenic and angiogenic potential in vitro, and evaluate its effects on implant osseointegration and surrounding bone regeneration in an ovariectomized (OVX) rat model.</div></div><div><h3>Methods</h3><div>In vitro studies were conducted to identify miRNAs exhibiting the greatest osteogenic and angiogenic potential among candidate miRNAs (miR-31, -34a, −146, −210, −218, and −31 + 210). Subsequently, the most effective miRNA was selected and locally administered to the bone matrix, where hydroxyapatite/tricalcium phosphate (HA/TCP)-coated titanium implants were placed in the femurs of OVX rats for in vivo studies. At 2, 4, and 8 weeks post-implantation, implant osseointegration, osteogenesis, angiogenesis of the matrix bone, and the initial fixation of the implant were evaluated using histological, genetic, radiological, and biomechanical assessments.</div></div><div><h3>Results</h3><div>miR-31 and miR-210 were strongly associated with osteogenesis, whereas miR-31 was strongly associated with angiogenesis. Moreover, the simultaneous administration of miR-31 and miR-210 resulted in the highest osteogenic potential among the miRNAs tested. In the OVX rat model, local administration of miR-31 + 210 significantly enhanced implant osseointegration, osteogenesis, angiogenesis within the bone matrix, and initial fixation of the implant compared to controls.</div></div><div><h3>Conclusion</h3><div>Local administration of miR-31 + 210 around HA/TCP-coated implants effectively improved implant osseointegration, the bone matrix environment, and initial fixation of implants in osteoporotic bone, likely by promoting osteogenesis and angiogenesis. This strategy holds promise as a novel regeneration therapy for enhancing implant fixation in patients with poor bone quantity.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101055"},"PeriodicalIF":3.5,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839204","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":"Recent progress in immunomodulation-based strategies for bone repair","authors":"Wang Yuqiang,&nbsp;Zhang Ziyan,&nbsp;Sun Xuedi,&nbsp;Piao Chengdong","doi":"10.1016/j.reth.2025.101054","DOIUrl":"10.1016/j.reth.2025.101054","url":null,"abstract":"<div><div>Bone regeneration is a highly coordinated process shaped by the interplay between immune responses and osteogenic mechanisms. Immune cells such as neutrophils, macrophages, T cells, and B cells dynamically regulate the local microenvironment through cytokine secretion and signaling pathways, thereby influencing osteogenesis, angiogenesis and bone remodeling, while dysregulated or prolonged inflammation can disrupt healing. Growing evidence has highlighted the potential of leveraging immunomodulation to enhance bone repair. This review synthesizes recent progress in immunoregulatory strategies by comparing cellular therapies, molecular interventions and biomaterial-based approaches in terms of their mechanisms, their effects on osteogenesis and angiogenesis, and their translational potential. Particular emphasis is placed on immune cell specific signaling pathways, biomaterial design parameters including surface topography, porosity, ion release and stiffness, and emerging technologies such as immune responsive hydrogels, programmable scaffolds and exosome based delivery systems. Current findings indicate that mesenchymal stem cells and regulatory T cells not only provide progenitor sources but also reshape the immune milieu through paracrine factors and exosomes; cytokines, small molecules, microRNAs and pro resolving mediators effectively modulate inflammatory cascades to promote vascularized bone formation; and immunomodulatory biomaterials enable spatiotemporal regulation of macrophage polarization, particularly the transition from the pro inflammatory M1 phenotype to the reparative M2 phenotype. Collectively, these advances highlight that bone repair is fundamentally an immunologically driven process, and integrating temporal immune regulation with emerging therapeutic platforms offers a promising pathway toward precise and personalized bone regeneration.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101054"},"PeriodicalIF":3.5,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839205","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":"Development of a digital analysis system for a novel 3D culture-based colony formation to detect malignantly transformed cells in human cell-based therapeutic products","authors":"Shinji Kusakawa ,&nbsp;Tingshu Yang ,&nbsp;Rumi Sawada ,&nbsp;Ryuji Kato ,&nbsp;Yoji Sato ,&nbsp;Satoshi Yasuda","doi":"10.1016/j.reth.2025.101052","DOIUrl":"10.1016/j.reth.2025.101052","url":null,"abstract":"<div><h3>Introduction</h3><div>The presence of malignantly transformed cells in human cell-based therapeutic products (hCTPs) is a significant safety concern. Although such cellular impurities in hCTPs can be assessed by detecting anchorage-independent growth using conventional soft agar colony formation (SACF) assays, the sensitivity of these assays is often insufficient. To overcome this limitation, we previously developed a novel tumorigenicity-associated testing method, the digital SACF (D-SACF) assay, which combines a partitioned culture of test cells to concentrate target cells with colony detection via image analysis. However, conventional soft agar culture involves complicated operations, such as preparing multilayered agar media and temperature control, and further technical optimization is required for the widespread adoption of the D-SACF assay.</div></div><div><h3>Methods</h3><div>In this study, we focused on a new culture system incorporating a three-dimensional (3D) culture method using a liquid medium containing the low-molecular-weight agar polymer LA717 in low-adhesion culture vessels. We initially confirmed conditions for the efficient high-density 3D culture of normal cells using LA717-supplemented medium in low-adhesion 96-well plates.</div></div><div><h3>Results</h3><div>Using human mesenchymal stem/stromal cells (MSCs) as a normal cell model and HeLa cells as a transformed cell model, we demonstrated that the new 3D culture system effectively maintained the dispersion of MSCs and prevented their aggregation, while transformed HeLa cells exhibited robust anchorage independence, thereby establishing the new liquid/low-molecular-weight agar colony formation (LACF) method as an alternative to SACF.</div></div><div><h3>Conclusions</h3><div>Finally, by systematizing the digital analysis system for the LACF assay (D-LACF assay), which streamlines the overall workflow from the performance evaluation of the test method to product testing and result interpretation, the limitations of the conventional soft agar-based D-SACF assay were addressed, and its practicality and utility were enhanced. This <em>in vitro</em> evaluation system is expected to provide a promising approach for improving the quality and safety of hCTPs.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101052"},"PeriodicalIF":3.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796775","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}