Tissue engineering and regenerative medicine最新文献

{"title":"Effect of hUCMSC-sEV-Loaded GelMA Microspheres on Pulp/Dentin Repair and Regeneration.","authors":"Xinping Lu, Huidan Deng, Ruotong Mai, Jingyi Kang, Quanjie Li, Huijia Li, Tingting Liang, Qiuxue Chen, Yu Wu","doi":"10.1007/s13770-026-00809-1","DOIUrl":"https://doi.org/10.1007/s13770-026-00809-1","url":null,"abstract":"<p><strong>Background: </strong>This study evaluated the biocompatibility of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hUCMSC) loaded in gelatin methacryloyl hydrogel microspheres (sEVs@GM-MS), and examined their effects on the proliferation and migration of human dental pulp stem cells (hDPSCs)/human umbilical vein endothelial cells (HUVECs), as well as their capacity to promote endothelial cell tube formation. Pulpotomy in a rat molar model was used to assess sEVs@GM-MS as a potential pulp-capping agent.</p><p><strong>Methods: </strong>sEVs@GM-MS were prepared and physicochemically characterized. In vitro assessments included live/dead staining, Cell Counting Kit-8 (CCK-8), migration assay and tube formation assay. In vivo, 7 and 14 days after pulpotomized with sEVs@GM-MS, GM-MS, iroot BP or without any pulp capping material, rat molars were evaluated using hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemical (IHC) staining.</p><p><strong>Results: </strong>GM-MS exhibited a porous surface via scanning electron microscopy. PKH67-labeled sEVs@GM-MS showed sustained release of sEVs. The cell proliferation, migration, tube formation in the sEVs@GM-MS group were significantly enhanced compared with those of the NC and GM-MS groups (p < 0.05). In rat pulpotomy model, sEVs@GM-MS group exhibited significant cell proliferation, angiogenesis, and reparative dentinogenesis with immunocytochemical localization of PCNA, CD31 and DMP-1 compared to NC and GM-MS groups (p < 0.05). Compared with the BP group, the sEVs@GM-MS group showed no significant difference in DMP-1 positive expression (p > 0.05).</p><p><strong>Conclusion: </strong>sEVs@GM-MS demonstrated excellent biocompatibility, sustained hUCMSC-sEV release, and enhanced pulp/dentin repair and regenaration, highlighting their potential as a pulp-capping agent.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPRC6A-Duox1 Axis Regulates the Hair Cycle Through H₂O₂ Generation.","authors":"Kkotnara Park, Areum Cho, Jung Min Park, Mee Sook Jun, Eunbi Ko, Soon-Sun Bak, Jung Min Suh, Kyoungmi Kim, Young Kwan Sung, Daekee Lee, Yun Soo Bae, Ji Won Oh","doi":"10.1007/s13770-026-00807-3","DOIUrl":"https://doi.org/10.1007/s13770-026-00807-3","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence suggests that G-protein-coupled receptor family C group 6 member A (GPRC6A) and Dual oxidase 1 (Duox1) mediate a non-classical testosterone signaling pathway. However, the molecular mechanism in which testosterone mediates the GPRC6A-Duox1 cascade in the hair cycle was unclear. Therefore, this study aimed to elucidate the molecular role of the testosterone-GPRC6A-Duox1 signaling axis in regulating hair cycle progression and testosterone-mediated hair loss.</p><p><strong>Methods: </strong>GPRC6A-deficient and Duox1-deficient keratinocytes were prepared and stimulated with testosterone to assess hydrogen peroxide (H₂O₂) generation. Apoptosis was evaluated in primary keratinocytes from GPRC6A knockout (KO), Duox1 KO, and wild-type (WT) mice. Hair growth cycle progression was examined by measuring anagen phase duration and hair length. Ki-67 expression was analyzed as a marker of the anagen phase. To validate the testosterone-GPRC6A-Duox1 signaling network in androgenetic alopecia, testosterone was topically applied for one week to the back skin of WT, Duox1 KO, and GPRC6A KO mice on postnatal day 31 (P31).</p><p><strong>Results: </strong>GPRC6A-deficient and Duox1-deficient keratinocytes failed to induce H₂O₂ generation in response to testosterone. Testosterone-dependent apoptosis in primary keratinocytes from GPRC6A KO and Duox1 KO mice was suppressed compared to keratinocytes from WT. The anagen phase of the hair growth cycle and hair lengths in GPRC6A KO and Duox1 KO mice were longer than WT consistent with the GPRC6A-Duox1 axis stimulating the anagen-to-catagen transition. The expression of Ki-67, a hallmark of the anagen phase, in GPRC6A KO and Duox1 KO mice was higher than that in WT. Duox1 KO and GPRC6A KO mice were resistant to testosterone-mediated hair loss, unlike WT.</p><p><strong>Conclusion: </strong>Taken together, these results suggest that the GPRC6A-Duox1 axis regulates natural hair cycles and testosterone-mediated hair loss.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intralesional Adipose-Derived Stem Cells Reverse Established Dermal Fibrosis and Modulate Angiogenesis-Related Readouts in a Murine Systemic Sclerosis Model.","authors":"Eunji Lee, Yeon Hee Ryu, Su Jin Lee, So Hyun Kwon, Suk-Ho Moon","doi":"10.1007/s13770-026-00811-7","DOIUrl":"https://doi.org/10.1007/s13770-026-00811-7","url":null,"abstract":"<p><strong>Background: </strong>Systemic sclerosis (SSc) is characterized by progressive dermal fibrosis and microvascular dysfunction, and no approved therapy reliably reverses established skin fibrosis or durably restores microvascular perfusion. Adipose-derived stem cells (ASCs) possess anti-fibrotic, immunomodulatory, and vascular-related parameters properties, but their therapeutic impact in a strictly therapeutic (rather than preventive) SSc-like setting remains incompletely defined.</p><p><strong>Methods: </strong>Bleomycin-induced systemic sclerosis model was induced in male C57BL/6 mice by daily subcutaneous bleomycin injections (100 μg) into dorsal skin for 28 days. On day 14, mice received a single intralesional injection of ASCs (1 × 10⁵ cells) or vehicle. At day 28, cutaneous perfusion was measured by laser Doppler perfusion imaging, and dorsal skin was analyzed by histology, hydroxyproline assay, RT-qPCR, and immunohistochemistry for CD34, α-SMA, and TNF-α. To support mechanistic interpretation, TGF-β1-stimulated dermal fibroblasts were co-cultured with ASCs and fibrosis-related gene expression was assessed.</p><p><strong>Results: </strong>Intralesional ASC administration significantly attenuated bleomycin-induced dermal fibrosis, reducing dermal thickness (244.0-163.5 μm) and collagen area fraction (87.2-62.8%). Hydroxyproline content decreased from 0.187 to 0.121 μg/mg tissue. ASC treatment also suppressed profibrotic and inflammatory transcripts (α-SMA ~ 3.99-fold, TGF-β1 ~ 6.07-fold, TNF-α ~ 7.48-fold, IL-6 ~ 2.36-fold vs. BLM + PBS) and increased vascular responses transcripts (VEGF ~ 2.65-fold, CD34 ~ 1.28-fold vs. BLM + PBS). ASC co-culture suppressed profibrotic activation of TGF-β1-stimulated fibroblasts, reducing profibrotic expression (α-SMA ~ 2.5-fold, TGF-β1 ~ 3.5 -fold, and COL1A1 ~ 2.7-fold).</p><p><strong>Conclusions: </strong>A single intralesional ASC injection alleviated established bleomycin-induced dermal fibrosis and was associated with vascular-related changes in fibrotic tissue. These effects may involve paracrine-mediated suppression of TGF-β1-driven fibroblast activation, supporting ASCs as a promising regenerative strategy for systemic sclerosis skin disease.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal Protocol for Differentiation of Human Tonsil-Derived Mesenchymal Stem Cells into Pancreatic β-like Cells.","authors":"Jiin Yang, Ha Yeong Kim, So Jeong Kim, Han Su Kim","doi":"10.1007/s13770-026-00806-4","DOIUrl":"https://doi.org/10.1007/s13770-026-00806-4","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus, characterized by β-cell dysfunction and loss, results in impaired insulin secretion and chronic metabolic complications. Mesenchymal stem cells represent a promising source for β-cell regeneration owing to their endodermal differentiation potential. This study optimized the differentiation of human tonsil-derived mesenchymal stem cells (TMSCs) into pancreatic β-like cells through the comparative evaluation of two signaling-based protocols.</p><p><strong>Methods: </strong>TMSCs were isolated from human tonsils, and passages 5-7 were used for characterization and β-like cell differentiation. Two protocols were tested in both two-dimensional (2D) and three-dimensional (3D) cultures: Protocol I induced direct differentiation into pancreatic β-like cells without sequential developmental stages, whereas Protocol II followed stepwise progression from definitive endoderm to pancreatic progenitors, and finally pancreatic β-like cells.</p><p><strong>Results: </strong>In 2D culture, cells cultured under protocol II maintained a typical morphology and high confluency, whereas cells cultured under protocol I displayed a thinner shape with reduced confluency. Protocol II effectively induced definitive endoderm differentiation, as demonstrated by the increased expression of SOX17, FOXA2, and CXCR4 at the mRNA and protein levels. Both protocols upregulated pancreatic progenitor (HNF6 and NGN3) and pancreatic β-cell markers (Insulin, NKX6.1, and PDX1), but protocol II consistently produced higher pancreatic β-cell marker expression, except for MafA. In 3D spheroid culture, insulin, PDX1, and MafA levels increased, with protocol II showing superior expression over protocol I. Additionally, differentiated cells exhibited glucose-responsive C-peptide secretion, indicating the acquisition of early β-cell-like functional properties.</p><p><strong>Conclusion: </strong>Stepwise, developmentally guided differentiation (Protocol II) more effectively directs TMSCs toward pancreatic β cell lineage commitment, highlighting the importance of stage specific signaling cues and supporting the potential of TMSCs for pancreatic β cell-based regenerative applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Probiotic-Adjunctive Vonoprazan-Amoxicillin Dual Therapy on Gut Microbiota and Clinical Symptoms in Helicobacter pylori Eradication.","authors":"YingYing Yang, ChunHui Lan, Zheng Jiang","doi":"10.1007/s13770-026-00803-7","DOIUrl":"https://doi.org/10.1007/s13770-026-00803-7","url":null,"abstract":"<p><strong>Background: </strong>This study evaluates the impact of Bacillus subtilis dual-strain enteric-coated capsules combined with vonoprazan-amoxicillin (VA) therapy on Helicobacter pylori (Hp) eradication rates, gastrointestinal symptoms, adverse events (AEs), and gut microbiota.</p><p><strong>Methods: </strong>60 Hp-positive adults were enrolled, allocated to probiotic (n = 30) or placebo (n = 30) groups. Both groups received a 14-day VA dual therapy, with the probiotic group additionally receiving a 28-day Bacillus subtilis dual-strain capsule regimen and the placebo group receiving matched placebos. Outcomes included Hp eradication rates (intention-to-treat [ITT]/per-protocol [PP] analyses), Gastrointestinal Symptom Rating Scale (GSRS) scores, AEs, antibiotic susceptibility, and gut microbiota changes (16S rRNA sequencing).</p><p><strong>Results: </strong>ITT analysis showed identical eradication rates (93.33%) in both groups; PP analysis revealed 96.67% (probiotic) versus 93.33% (placebo). The probiotic group exhibited significantly lower GSRS scores at weeks 4 (T2) and 8 (T3), particularly for diarrhea and acid reflux, with milder AEs (severity score: 5). Probiotic supplementation reduced Hp resistance to metronidazole (26.67% vs. 60.00%) without affecting other antibiotics. Microbiota analysis demonstrated post-eradication reductions in gastric pathogens (e.g., Helicobacter) and increased beneficial bacteria (e.g., Lactobacillus). The probiotic group showed faster restoration of gut α-diversity (higher at T2), enriched butyrate producers (e.g., Blautia, Anaerobutyricum), and decreased opportunistic pathogens (e.g., Klebsiella).</p><p><strong>Conclusions: </strong>Although Bacillus subtilis supplementation did not enhance Hp eradication rates, it significantly improved gastrointestinal symptoms, reduced AEs, increased Hp susceptibility to metronidazole, and accelerated microbiota recovery, supporting its role in microbiome modulation during Hp eradication therapy.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Cell Isolation for Adipose- and Synovium Derived Mesenchymal Stem Cells from Infrapatellar Fat Pad.","authors":"Yeeun Kim, Hee-Woong Yun, Sujin Noh, Sumin Lim, Jun Young Chung, Jae-Young Park, Do Young Park","doi":"10.1007/s13770-026-00805-5","DOIUrl":"https://doi.org/10.1007/s13770-026-00805-5","url":null,"abstract":"<p><strong>Background: </strong>The infrapatellar fat pad (IFP) is a rich source of mesenchymal stem cells (MSCs) with dual contributions from adipose and synovial tissues. The heterogeneity of IFP-derived MSCs and the lack of standardized isolation protocols, however, hinder consistent therapeutic outcomes. This study aimed to optimize collagenase-based isolation protocols for IFP-MSCs, with a focus on the effects of enzyme concentration and treatment duration on tissue digestion, cell origin, viability, and functional properties.</p><p><strong>Methods: </strong>IFP tissues harvested from patients undergoing knee arthroscopy were enzymatically digested using various collagenase concentrations (0.1-2%) and incubation times (2-48 h). Histological, immunohistochemical, flow cytometric, and functional assays were performed to evaluate tissue degradation, surface marker expression, colony-forming ability, and trilineage differentiation.</p><p><strong>Results: </strong>Milder digestion conditions (2 h, 0.2-0.4% collagenase) preferentially extracted synovial membrane MSCs (CD55⁺ cells) and supported higher CFUs and chondrogenic/osteogenic differentiation. In contrast, prolonged digestion (48 h) led to increased cell yields and adipogenic differentiation, but reduced cell viability and percentage of synovial marker expression.</p><p><strong>Conclusion: </strong>In conclusion, enzymatic digestion parameters critically influence the cellular composition and regenerative potential of IFP-MSCs. Optimizing collagenase treatment conditions allows for a more selective, lineage-based MSC harvest, offering a practical strategy for tailored regenerative utilization of IFP-MSCs.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Amniotic Fluid Stem Cell-mediated Biomechanical Restoration of Urinary Continence in Rats.","authors":"Shing-Hwa Lu, Shiaw-Min Hwang, Navneet Kumar Dubey, Ming-Song Tsai, Tien-Fu Yun, Jiunn-Wang Liao","doi":"10.1007/s13770-026-00802-8","DOIUrl":"https://doi.org/10.1007/s13770-026-00802-8","url":null,"abstract":"<p><strong>Background: </strong>Stress urinary incontinence (SUI) adversely impacts millions worldwide due to weakened pelvic floor muscles and urethral sphincter dysfunction. To date, there is a lack of effective non-surgical treatment for SUI, and no clear consensus has been reached on the optimal stem cell source under regenerative therapy. Existing studies have shown no precise molecular mechanisms underlying stem cell-mediated external urethral sphincter (EUS) regeneration. Therefore, we investigated the regenerative and reparative potential of our clinical-grade human amniotic fluid stem cells (hAFSCs) for treating SUI.</p><p><strong>Methods: </strong>We determined the immunophenotype, multi-differentiation potential, and secretome of AFSCs. Treated animals were grouped into sham, UI, phosphate buffer saline, and hAFSC groups. Pudendal nerve injury was created to induce SUI in female rats and treated with hAFSCs by administering them into the external urethral sphincter.</p><p><strong>Results: </strong>Isolated AFSCs showed trilineage potential and expressed neuronal-specific markers such as Nestin, Tuj-1, MAP2, and GFAP. hAFSCs-treated group showed significantly (p < 0.01) improved leak point pressure, intercontractile interval, and total muscle cell proliferation numbers. hAFSCs showed elevated levels of VEGF, IL-8, TIMP-1, and TIMP-2. Histological assessment of bladder tissues reveals that hFASCS ameliorated lower ulceration and edema. Immunofluorescence staining and myogenic differentiation markers, i.e., Myf5, Myogenin, and MyoD, indicate the bladder tissue regenerating potential of hAFSCs. No hAFSC trafficking was observed in other tissues and organs.</p><p><strong>Conclusion: </strong>These findings highlight hAFSCs' potential as a novel therapy for SUI, warranting more extensive clinical trials to optimize dosing and long-term efficacy while addressing scalability and safety challenges in translating this regenerative approach to clinical practice.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regenerative effects of myogenic gene transfected MSC derived exosomes on radiation esophagitis.","authors":"Min-Kyung Kim, In Gul Kim, So Young Eom, Yewon Kim, Jin-A Kim, Jungirl Seok, Seok Chung, Hye-Joung Kim, Eun-Jae Chung","doi":"10.1007/s13770-026-00795-4","DOIUrl":"https://doi.org/10.1007/s13770-026-00795-4","url":null,"abstract":"<p><strong>Background: </strong>Radiation esophagitis is a common adverse effect of radiotherapy for head and neck cancers, and is marked by irreversible damage and fibrosis of esophageal muscle tissue. Although mesenchymal stem cell (MSC) therapy is emerging as a promising approach for tissue regeneration, clinical translation remains challenging due to issues with cell viability and differentiation in vivo. This study evaluates the regenerative efficacy of exosomes derived from MSCs transfected with myogenic genes (MyoD, Myogenin, Myf6, referred to as Myo-MIX) using a murine model of radiation-induced esophageal fibrosis.</p><p><strong>Methods: </strong>Human adipose-derived MSCs were transfected with Myo-MIX plasmids by electroporation, and exosomes were collected from conditioned media using ExoQuick. Nanoparticle tracking analysis and transmission electron microscopy were employed to characterize exosomal size and morphology. A mouse model of localized radiation-induced esophageal injury (10 Gy × 2 fractions) was generated and followed by intramuscular administration of Myo-MIX exosomes. Regenerative and anti-fibrotic outcomes were examined through Masson's trichrome staining, immunohistochemistry (α-SMA, Calponin, CD68), and quantitative RT-PCR.</p><p><strong>Results: </strong>Treatment with Myo-MIX exosomes resulted in a pronounced decrease in fibrosis and inflammatory response compared to PBS-treated controls and naïve MSC-exosome groups. Enhanced restoration of muscular architecture was observed, accompanied by elevated expression of Calponin and α-SMA, and a reduction in CD68 + macrophage infiltration. Gene expression profiling indicated increased levels of myogenic and anti-fibrotic markers in the Myo-MIX exosome-treated group.</p><p><strong>Conclusion: </strong>Exosomes from myogenic gene-transfected MSCs significantly enhance esophageal muscle regeneration and attenuate fibrosis after radiation-induced damage. This cell-free therapeutic approach holds potential as a novel and practical strategy for addressing radiation esophagitis in patients receiving radiotherapy for head and neck malignancies.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-Drug Stent with Sirolimus and WKYMVm Promotes Endothelialization and Limits Hyperplasia.","authors":"Yu Jeong Jin, Dae Sung Park, Myung Ho Jeong, Doo Sun Sim, Mi Hyang Na, Chan Woo Kim, Jeong Ha Kim, Hae Jin Kee, Young Joon Hong, Kyung Hoon Cho, Dae Young Hyun, Seok Oh, Jeong Hun Kim, Dong-Weon Lee","doi":"10.1007/s13770-025-00791-0","DOIUrl":"10.1007/s13770-025-00791-0","url":null,"abstract":"<p><strong>Background: </strong>Conventional drug-eluting stents suppress neointimal hyperplasia but delay re-endothelialization, raising long-term safety concerns. This study developed and evaluated a sirolimus-WKYMVm eluting stent (S-WES) to simultaneously promote re-endothelialization and suppress neointimal hyperplasia.</p><p><strong>Methods: </strong>Sirolimus-eluting stents (SES), WKYMVm-eluting stents (WES), and S-WES were fabricated using electrospray. Surface morphology was characterized via scanning electron microscopy (SEM), and in vitro drug-release kinetics were determined using high-performance liquid chromatography. Biological efficacy was assessed using human umbilical vein endothelial cell (HUVEC) and smooth muscle cell (SMC) assays. In vivo performance was evaluated over 4 weeks, followed by optical coherence tomography (OCT) and histopathological analysis.</p><p><strong>Results: </strong>SEM analysis showed that S-WES had a uniform, crack-free polymer coating. Each stent was consistently loaded with sirolimus (105.15 ± 25.54 μg) and WKYMVm (1.07 ± 0.18 μg), yielding a dual drug-release profile. WKYMVm was almost completely released within 7 days, whereas sirolimus showed sustained release (day 1: 22.43 ± 5.32%, day 28: 94.38 ± 4.11%). In vitro assays showed that sirolimus suppressed SMC migration and HUVEC proliferation, while WKYMVm significantly enhanced HUVEC proliferation. In vivo OCT revealed reduced neointimal hyperplasia in the S-WES group (29.64 ± 8.66 μm²) compared with SES (34.65 ± 7.50 μm²; p = 0.041). Histopathology and immunohistology showed reduced stenosis ratio (28.39 ± 6.84%), decreased α-SMA expression, and increased VE-cadherin, CD31-positive endothelial coverage in the S-WES group.</p><p><strong>Conclusion: </strong>The sirolimus-WKYMVm dual-drug stent enhances re-endothelialization and inhibits neointimal hyperplasia, thereby offering a promising strategy for improving the efficacy and long-term safety of cardiovascular stents.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"381-394"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Amniotic Mesenchymal Stromal Cells Promote Bone Regeneration via Regulating Ameloblastoma-Derived-Bone Marrow Mesenchymal Cells Crosstalk and Autophagy in Ameloblastoma Microenvironment.","authors":"Yuhuan Xiao, Xiaofeng Fu, Weina Zhou, Jin Li, Bin Yan, Fei Jiang","doi":"10.1007/s13770-025-00789-8","DOIUrl":"10.1007/s13770-025-00789-8","url":null,"abstract":"<p><strong>Background: </strong>Growing evidence validates the vital function of mesenchymal stem cells (MSCs) in tumor development. Our previous findings have illustrated the role of MSCs in the invasion and recurrence of ameloblastoma. Stem cells can be transplanted to release paracrine factors in the tumor microenvironment (TME) to inhibit tumor progression and recurrence. The paracrine function of human amniotic mesenchymal stromal cells (HAMSCs) benefits bone regeneration. However, the dual function of HAMSCs in inhibiting tumor progression and promoting bone regeneration in the TME remains unknown.</p><p><strong>Methods: </strong>To analyze the role of HAMSCS in the cross-talk between mesenchymal ameloblastoma-derived cells (M-AMCs), human bone marrow mesenchymal stem cells (HBMSCs), and HAMSCs, an in vitro co-culture system of M-AMCs, HBMSCS, and HAMSCS was prepared. An in vivo ectopic transplantation model was employed further to detect the therapeutic effect of HAMSCs on bone regeneration.</p><p><strong>Results: </strong>A high-level basal autophagy was detected in the stroma of ameloblastoma. In the in vitro co-culture models, M-AMCs suppressed the proliferation, differentiation, migration, and autophagy of HBMSCs, and conversely, HBMSCs promoted the above phenotypes of M-AMCs. HAMSCs promoted the proliferation, differentiation, migration and autophagy of the co-cultured HBMSCs. Additionally, HAMSCs mediated the cross-talk between M-AMCs and HBMSCs. The in vivo ectopic transplantation model indicated that transplanted HAMSCs promoted bone regeneration by inhibiting the growth of M-AMCs and enhancing autophagy, as well as osteogenesis in bone defects of mice.</p><p><strong>Conclusions: </strong>The interaction of M-AMCs and HBMSCs may be associated with ameloblastoma recurrence. HAMSCs regulate the cross-talk between M-AMCs and HBMSCs to increase the autophagic level in the TME, thus inhibiting the progression and recurrence of ameloblastoma and promoting bone regeneration. Therefore, HAMSC-based therapy provides an alternative to facilitate bone regeneration and repair of ameloblastoma-induced bone defects.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"491-504"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}