Regenerative Therapy最新文献

{"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}

{"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":"2026-03-01","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":"Which trajectory should we choose? — Defining safe entry–target pathways and underlying femoral morphology for bone marrow injection in osteonecrosis of the femoral head","authors":"Ken Tashiro ,&nbsp;Yasuhiro Homma ,&nbsp;Yuto Kawamura ,&nbsp;Ryuji Okuno ,&nbsp;Eiji Iwasaki ,&nbsp;Fumihiro Mukasa ,&nbsp;Koju Hayashi ,&nbsp;Taiji Watari ,&nbsp;Tomonori Baba ,&nbsp;Muneaki Ishijima","doi":"10.1016/j.reth.2026.101084","DOIUrl":"10.1016/j.reth.2026.101084","url":null,"abstract":"<div><h3>Introductions</h3><div>Bone marrow aspiration concentrate (BMAC) injection is a promising joint-preserving treatment for osteonecrosis of the femoral head (ONFH). However, the procedure remains unstandardized, and iatrogenic complications, including subtrochanteric fractures, have been reported. Despite its growing clinical adoption, no studies have modeled this procedure in a representative cohort to evaluate its technical safety. This study aimed to establish a morphological basis for safer and more standardized needle placement by identifying entry–target combinations that provide the safest trajectories, and determining the proximal femoral parameters influencing the permissible insertion angle.</div></div><div><h3>Methods</h3><div>Forty hips without collapse or deformity from 40 patients with ONFH (20 males and 20 females) were retrospectively analyzed using computed tomography-based three-dimensional reconstructions. Four entry levels (A–D) and four femoral head target points (center–center, center–lateral, anterior–center, anterior–lateral) were defined. Needle trajectories were reconstructed, and the permissible insertion angle was defined as the range within which cortical perforation did not occur. Linear regression analyses were conducted to identify morphological factors associated with the permissible insertion angle.</div></div><div><h3>Results</h3><div>Six entry–target combinations achieved a 100% needle passage rate, representing the safest configurations for BMAC injection. Among these, the anterior–center target was the most accessible, allowing safe insertion at three different entry levels. The widest permissible insertion angle was observed when targeting the center–center region from entry level D (18.1° ± 3.7°). Morphological analysis revealed that a smaller minimum femoral neck diameter and greater femoral anteversion were independently associated with a narrower permissible insertion angle. Female patients demonstrated significantly narrower safe angular ranges than male patients across all entry–target combinations.</div></div><div><h3>Conclusion</h3><div>This study quantitatively identified six safe entry–target combinations and key morphological determinants influencing the permissible insertion angle. These findings provide practical anatomical reference data to support safer, morphology-based planning for ONFH treatment.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101084"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147356060","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":"From scaffold to function: A systematic review on dLECM-based hydrogels for liver tissue engineering — Fabrication, properties, and translational applications","authors":"Ziba Majidi ,&nbsp;Mohammad Mahdi Sarvi ,&nbsp;Mohammad Aref Rajabi ,&nbsp;Houran Firouzian ,&nbsp;Iman Seyhoun ,&nbsp;Masoumeh Majidi Zolbin","doi":"10.1016/j.reth.2025.11.006","DOIUrl":"10.1016/j.reth.2025.11.006","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Liver tissue engineering is a rapidly advancing field aiming to address the critical shortage of donor organs and improve &lt;em&gt;in vitro&lt;/em&gt; models for drug screening and disease modeling. Decellularized liver extracellular matrix (dLECM)-based hydrogels have emerged as a leading biomaterial platform due to their ability to preserve the native biochemical composition, microstructure, and biomechanical cues of the liver microenvironment. This systematic review aims to comprehensively evaluate the methodologies, physicochemical properties, biological performance, and translational applications of dLECM-derived hydrogels in liver tissue engineering, with a focus on fabrication protocols, functional outcomes, and challenges toward clinical implementation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A systematic search was conducted in accordance with PRISMA 2020 guidelines across PubMed, Scopus, Google scholar and Web of Science. A total of 74 studies were included after screening 536 records identified from databases. Data were extracted on tissue source, decellularization techniques, dECM solubilization, hydrogel formulation, crosslinking methods, physicochemical characterization, and &lt;em&gt;in vitro&lt;/em&gt;/&lt;em&gt;in vivo&lt;/em&gt; functional outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The majority of studies utilized porcine or rodent livers, with immersion/agitation and vascular perfusion as the primary decellularization methods. Sodium dodecyl sulfate (SDS), Triton X-100, and ammonium hydroxide were the most common detergents, often combined with enzymatic treatments (e.g., DNase, trypsin) to enhance nuclear removal. dLECM was predominantly solubilized using pepsin in acidic conditions (acetic acid or HCl) and reconstituted into hydrogels via thermal gelation at 37 °C. The resulting hydrogels demonstrated excellent biocompatibility, supporting high viability and enhanced functional activity—including albumin secretion, urea synthesis, and expression of hepatic markers (e.g., CYP450, CK18, AFP)—in primary hepatocytes, HepG2 cells, and stem cell-derived hepatocyte-like cells. Advanced applications such as 3D bioprinting, organoid culture, and &lt;em&gt;in vivo&lt;/em&gt; transplantation in liver injury models (e.g., CCl&lt;sub&gt;4&lt;/sub&gt;-induced fibrosis, acute liver failure) further highlight the therapeutic potential of these biomaterials. However, significant heterogeneity was observed in decellularization efficacy, residual DNA content (ranging from 1.04 % to 21.74 ng/mg), and mechanical characterization, with many studies lacking standardized reporting of storage modulus (G′) or gelation kinetics.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;dLECM-based hydrogels represent a highly promising and biomimetic platform for liver tissue engineering, capable of supporting complex cellular functions and regenerative outcomes. Despite significant progress, standardization of fabrication protocols, comprehensive physicochemical characterization, and long-term &lt;em","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101041"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578351","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":"2026-03-01","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":"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":"2026-03-01","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":"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":"2026-03-01","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":"PET/EVOH nonwoven fabrics support in vitro expansion of mesenchymal stem cells with high differentiation potential","authors":"Yu-Min Chen ,&nbsp;Chihoko Tokoda ,&nbsp;Yasuhiko Tabata","doi":"10.1016/j.reth.2025.101046","DOIUrl":"10.1016/j.reth.2025.101046","url":null,"abstract":"<div><div>Cell expansion under three-dimensional (3D) condition has been shown to better preserve cellular properties by mimicking the native microenvironment, thereby creating a more physiologically relevant culture system. This study investigated the capacity of a three-dimensional nonwoven polyethylene terephthalate (PET)/ethylene vinyl alcohol (EVOH) scaffold as a 3D substrate for large-scale expansion of mesenchymal stem cells (MSC). A seven-fold increase in cell number was observed after 14 days of cultivation, and cells were well distributed with an efficient infiltration within scaffolds based on the hematoxylin and eosin (H&amp;E) staining. A high cell survival and pertaining of metabolic activity were demonstrated by live/dead and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) stainings, respectively. The preservation of MSC properties was confirmed by their differentiation potential toward osteogenic, adipogenic, and chondrogenic lineages. Both <em>in situ</em> differentiation of cell-expanded scaffolds and the subsequent differentiation after cell retrieving from scaffolds revealed the successful responsiveness of expanded MSC to lineage-specific stimuli. These findings suggest the potential of this PET/EVOH scaffold as the 3D culture substrate enabling efficient MSC proliferation while maintaining key functional properties.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101046"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691063","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}