Tissue engineering and regenerative medicine最新文献

{"title":"Recent Progress of Dopamine-Modified Tissue Adhesives for Biomedical Applications in Underwater Environments.","authors":"Chong-Su Cho, Gi-Yeon Han, Eun Byul Koh, Yo-Han Kim, Yeon Ho Je, Hyun-Joong Kim","doi":"10.1007/s13770-026-00804-6","DOIUrl":"10.1007/s13770-026-00804-6","url":null,"abstract":"<p><strong>Background: </strong>Underwater adhesion of polymeric adhesives is highly desirable in specific applications such as wound dressings, wearable devices, bioelectronic devices, biosensors, and water pipeline leakage repairing. However, underwater bonding is considerably different from bonding in air because interfacial water molecules substantially weaken the intimate contact adhesion between the adhesive and submerged surfaces, thus significantly limiting the application of adhesives in various fields.</p><p><strong>Method: </strong>This review was compiled by searching relevant references on PubMed database (before April 2025) based on selected keywords.</p><p><strong>Results: </strong>Recently, many wet adhesion technologies and diverse and flexible adhesive materials have been employed to address the weak adhesion strengths and inferior mechanical properties in underwater environments. Among several strategies, mussel-inspired catechol-based underwater adhesion has gained the attention of scientists because mussel-inspired tissue adhesives (TAs) demonstrate numerous advantages including many interactions with substrates, various designs of some interesting smart TAs, and excellent adhesion based on several interfacial interactions dominated by 3,4-dihydroxyphenylalanine, a catecholic amino acid in mussel adhesive proteins.</p><p><strong>Conclusion: </strong>We discuss the mechanism of catechol-based underwater adhesion, classification of underwater adhesives, and characteristics, applications, advantages, and disadvantages of dopamine (DA)-modified polymeric TAs. Furthermore, we review stimuli-responsive TAs and the essential factors affecting the adhesions of DA-modified TAs in underwater environments. Finally, we discuss some current technical challenges and future perspectives for underwater adhesion.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"617-638"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487315","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 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":"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":"667-679"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323422/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liraglutide Promoted Osteogenic Differentiation of Dental Pulp Stem Cells via H3K18 Lactylation-Dependent DSPP Activation.","authors":"Ruixue Li, Jing Zhang, Xixi Song, Lulu Han, Mingyan Yao","doi":"10.1007/s13770-026-00801-9","DOIUrl":"10.1007/s13770-026-00801-9","url":null,"abstract":"<p><strong>Background: </strong>Dental pulp stem cells (DPSCs) are critical for periodontal tissue regeneration, yet their therapeutic potential is limited by suboptimal osteogenic differentiation. Liraglutide (LIRA), a glucagon-like peptide-1 receptor agonist, exhibits anti-inflammatory and bone-protective properties. This study aimed to investigate the modulatory effects of LIRA on DPSCs proliferation and osteogenic differentiation.</p><p><strong>Methods: </strong>DPSCs were treated with LIRA to assess proliferation and osteogenic differentiation using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine staining, alkaline phosphatase (ALP), and alizarin red S (ARS) assays. Histone lactylation levels (total lactylation and H3K18la) were quantified by Western blot. Chromatin immunoprecipitation (ChIP) and dual-luciferase assays evaluated H3K18la enrichment at the dentin sialophosphoprotein (DSPP) promoter. DSPP overexpression was used in rescue experiments to validate the role of the H3K18la-DSPP axis.</p><p><strong>Results: </strong>LIRA significantly enhanced DPSC proliferation and osteogenic differentiation, as evidenced by increased ALP activity, mineralization nodules, and upregulated osteogenic markers (DMP1, DSPP, RUNX2, OCN, OPN). LIRA elevated global lactylation and H3K18la levels, with ChIP assays showing H3K18la enrichment specifically at the DSPP promoter. Dual-luciferase and RT-qPCR confirmed LIRA-induced DSPP transcriptional activation. Oxamate reversed LIRA's effects, while Nala amplified them. DSPP overexpression rescued oxamate-mediated suppression of osteogenesis, confirming the H3K18la-DSPP regulatory mechanism.</p><p><strong>Conclusion: </strong>This study demonstrates that LIRA promotes DPSC osteogenesis via histone lactylation-mediated DSPP transcriptional activation. The H3K18la-DSPP axis represents a novel metabolic-epigenetic pathway for enhancing periodontal regeneration.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"573-582"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481680","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":"Engineering Mesenchymal Stem Cells with Nanomaterials for Tumor Microenvironment Regulation and Precision Therapy.","authors":"Dong-Yong Hong, Jieun Han, Wooram Park","doi":"10.1007/s13770-026-00794-5","DOIUrl":"10.1007/s13770-026-00794-5","url":null,"abstract":"<p><strong>Background: </strong>The tumor microenvironment (TME) is a major obstacle to effective cancer therapy, driving tumor progression, metastasis, and resistance to conventional treatments. Mesenchymal stem cells (MSCs) have attracted increasing interest as therapeutic vehicles due to their intrinsic tumor-homing capability; however, the therapeutic efficacy of unmodified MSCs remains limited.</p><p><strong>Methods: </strong>This review examines recent engineering strategies for enhancing MSC therapeutic functionality in TME modulation and precision cancer therapy. Relevant literature was surveyed with focus on nanotechnology-enabled approaches. We analyze key TME features including hypoxia, immunosuppression, and physical barriers, and how various engineering strategies address these challenges.</p><p><strong>Results: </strong>Engineered MSCs have been successfully transformed into therapeutic \"bio-factories\" through genetic modification, enabling sustained secretion of cytokines, enzymes, or therapeutic proteins. In parallel, payload-based strategies have established MSCs as effective \"Trojan horse\" carriers for nanomaterials, chemotherapeutic agents, and oncolytic viruses, allowing precise delivery and active remodeling of the TME. These approaches collectively enhance tumor targeting, therapeutic efficacy, and spatial control within solid tumors.</p><p><strong>Conclusion: </strong>The integration of MSC biology with nanotechnology provides a powerful platform for regulating the TME and achieving precision oncology. While challenges related to safety, protumorigenic effects, and manufacturing scalability remain, recent advances are rapidly addressing these barriers. Engineered MSC-based therapies hold great promise to revolutionize cancer treatment and overcome the longstanding challenges of solid tumor therapy.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"505-520"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202872","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":"Rapid and Efficient Combined Decellularization with Physical, Chemical and Enzymatic Treatment for Production of Bovine-Derived Meniscal Implant to Replace Damaged Meniscus.","authors":"Young-Bock Shim, Sang Hoon Lee, YoungWoo Ryu, Sang Hyun Jung, Shin Young Park, Yu Jin Lee, Hong Hee Jung, Dae Hyeok Yang, Heung Jae Chun","doi":"10.1007/s13770-026-00796-3","DOIUrl":"10.1007/s13770-026-00796-3","url":null,"abstract":"<p><strong>Background: </strong>Xenogeneic menisci offer a promising biomaterial with high biocompatibility, closely resembling the native meniscus. However, to enable clinical application in humans, decellularization is essential to remove cellular components that may trigger graft rejection.</p><p><strong>Method: </strong>We developed a combined decellularization protocol for bovine-derived meniscus tissue, integrating physical stimulation (sonication and vacuum), chemical treatments (hypotonic and hypertonic solutions, and sodium dodecyl sulfate [SDS]), and enzymatic digestion (trypsin and nucleases). The decellularization efficiency was confirmed not only by DNA reduction rate, but also by residual DNA, DNA fragmentation and histology. Subsequently, cytotoxicity, biocompatibility, and mechanical properties were assessed.</p><p><strong>Results: </strong>This combined decellularization achieved a DNA removal efficiency of up to 94.94%, enabled rapid decellularization within 5 days, and preserved collagen content, resulting in a high-quality xeno meniscal implant (XMI).</p><p><strong>Conclusion: </strong>The XMI produced through this combined decellularization process demonstrates strong potential as a scaffold for the treatment of meniscal injuries.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"537-550"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459559","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":"Biomimetic Constructs for Achilles Tendon Regeneration and their Translation to Human Medicine.","authors":"Emine Berfu Ozmen, David E Anderson, Andrew Ward, Madhu Dhar","doi":"10.1007/s13770-026-00799-0","DOIUrl":"10.1007/s13770-026-00799-0","url":null,"abstract":"<p><strong>Background: </strong>Achilles tendon injuries are among the most common lower-body tendon injuries, often resulting fromoveruse and repetitive motion. Current treatments, ranging from conservative therapies to biological grafts, have drawbacks, including limited regenerative capacity and the risk of graft rejection. To overcome these challenges, tissue engineering shows growing promise for Achilles tendon regeneration, with ongoing research focused on developing biomimetic constructs that utilize various materials and biologics. Since every tendon has unique biomechanical and physiological characteristics, it is crucial to conduct individualized evaluations through detailed research and to address key considerations for clinical translation.</p><p><strong>Methods: </strong>This review focuses explicitly on advances in Achilles tendon tissue engineering for human medicine, assessing constructs made from natural, synthetic, and composite materials with/without biologics and discussing their clinical translation. Studies were searched in the PubMed database and Google Scholar, using the most relevant keywords, such as \"Achilles tissue engineering\", \"Achilles biomimetic constructs\", \"Biomaterials for Achilles tendon\", and \"Clinical translation\".</p><p><strong>Results: </strong>Biomimetic constructs developed from various polymers and their combinations, when integrated with stem cells, demonstrate promising potential to reconstruct tissue microenvironments in vitro and to facilitate tissue repair and biomechanical functions in vivo. Carefully developing each element, including appropriate material structures, is essential for optimizing cell responses, biomechanical properties, and tissue repair in the Achilles tendon. Although the in vitro and in vivo advances reviewed in the paper contribute to clinical research, further studies with reproducible, long-term outcomes are needed to make the constructs clinically applicable in human medicine.</p><p><strong>Conclusion: </strong>Achilles tissue engineering continues to progress, driven by a deeper understanding of the injuries and the integration of regenerative tools. Furthermore, clinical considerations, such as long-term in vivo follow-up to assess biocompatibility and functional recovery, will be critical to achieving clinical outcomes.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"521-536"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463967","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":"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":"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":"597-612"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212833/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical and Mechanical Signal Differentially Contribute to Survival in Surface-Modified Cell Model.","authors":"Seoyoung Jang, Tong In Oh, Wook Park, EunAh Lee","doi":"10.1007/s13770-026-00800-w","DOIUrl":"10.1007/s13770-026-00800-w","url":null,"abstract":"<p><strong>Background: </strong>Regenerative cell sources such as bone marrow-multipotent stem cells (BM-MSCs) face poor survival after transplantation due to shear stress and anoikis in attachment-deprived conditions. Cell surface modification with type I collagen (Col I) may enhance cell survival in anoikis-inducing environment by mimicking cell-ECM interactions and activating Akt signaling. However, the relative contributions of biochemical versus mechanical signalling remain unclear.</p><p><strong>Methods: </strong>BM-MSCs were surface-modified with 2, 4, or 8 layers (L) of Col I and cultured on poly-2-hydroxyethyl methacrylate-coated vessels for 3 days. Col I retention, Akt activation, and cytoskeletal changes were analyzed by immunofluorescence. YAP nuclear translocation was measured to assess mechanotransduction.</p><p><strong>Results: </strong>Col I persisted up to 10 h in 4L and 8L groups but not in 2L. All surface-modified groups showed membrane-localized Akt phosphorylation, while controls did not. Only the 8L group demonstrated significant anoikis resistance from day 1, exhibiting distinct ring-like actin arrangement within 2 h and enhanced YAP nuclear localization, indicating activation of mechanotransduction-associated responses.</p><p><strong>Conclusions: </strong>All surface-modified groups showed Akt phosphorylation, indicating biochemical signaling. The 4L group exhibited significantly higher survival by day 2, suggesting sustained biochemical signaling promotes survival. The 8L group showed superior survival from day 1 with increased YAP translocation and actin reorganization, demonstrating that mechanotransduction may contribute to an early survival advantage. This cell model enables differential investigation of biochemical and mechanical effects on cell survival.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"561-571"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459512","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":"Development of Lung Mimics Using Homogeneous Pluripotent Stem Cells in Deep-Well Plate with Antioxidant-Enriched Media for Drug Screening and Infectious Disease Research.","authors":"In-Su Park, Ji-Young Oh","doi":"10.1007/s13770-026-00793-6","DOIUrl":"10.1007/s13770-026-00793-6","url":null,"abstract":"<p><strong>Background: </strong>Organoids are three-dimensional (3D) in vitro cell culture systems that grow and self-organize, with cells differentiating into functional types and forming miniature structures that replicate the architecture and function of in vivo organs. While the need for standardized organoid culture systems has been widely emphasized, the production of functionally complex and scalable lung organoids remains a significant challenge.</p><p><strong>Methods: </strong>Here, we present a scalable lung organoid production platform using a 96-deep-well format with organoids derived from induced pluripotent stem cells (iPSCs). iPSCs were first differentiated into definitive endoderm (DE), followed by anterior foregut endoderm (AFE) in a two-dimensional (2D) culture system. The AFE cells were then transferred into deep wells to generate alveolar epithelial cells (AECs), and subsequently differentiated into SFTPA-positive lung cells within 3D organoids over a 15-day period.</p><p><strong>Results: </strong>This new culture platform enables single cells to self-organize into organoids in a serum-free, antioxidant-enriched medium using a 96-deep-well plate. Compared to conventional organoid culture methods, this system significantly improves the consistency, uniformity, and reproducibility of organoid formation.</p><p><strong>Conclusion: </strong>Notably, organoids generated in deep wells are functionally comparable to those cultured in Matrigel, but offer enhanced uniformity-an essential improvement for reliable drug screening applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"551-560"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435714","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":"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":"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":"583-596"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212885/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}