Tissue engineering and regenerative medicine最新文献

{"title":"MSC-Derived Small Extracellular Vesicles Alleviate Renal Fibrosis in Hyperuricemic Nephropathy via Suppression of Epithelial Mesenchymal Transition.","authors":"Benshuai You, Haitao Hu, Jing Wei, Yun Xu, Chenglin Zhou","doi":"10.1007/s13770-026-00849-7","DOIUrl":"https://doi.org/10.1007/s13770-026-00849-7","url":null,"abstract":"<p><strong>Background: </strong>Hyperuricemic nephropathy (HN) arises from excessive accumulation of uric acid, leading to subsequent renal injury. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) have demonstrated beneficial effects in promoting tissue repair across various injury models. However, their potential therapeutic role in HN remains unknown.</p><p><strong>Methods: </strong>We isolated and characterized MSC-sEVs by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. A rat model of HN was established by daily administration of adenine and potassium oxonate for three weeks, after which MSC-sEVs were intravenously injected. Renal function, histopathological changes, and fibrotic markers were assessed, while the involvement of epithelial-mesenchymal transition (EMT) was examined both in vivo and in UA-treated HK-2 cells. Regenerative and anti-fibrotic outcomes were examined through Masson's trichrome staining and immunohistochemistry (α-SMA).</p><p><strong>Results: </strong>Rats with HN exhibited significant renal dysfunction and marked interstitial fibrosis. MSC-sEVs treatment significantly improved renal function, as evidenced by reduced serum creatinine and blood urea nitrogen, and attenuated tubulointerstitial fibrosis, collagen deposition, and α-SMA expression in HN rats. Mechanistically, UA induced a classic EMT phenotype in renal tubular cells in vivo and in vitro, characterized by downregulation of E-cadherin and upregulation of N-cadherin and vimentin, all of which were markedly reversed by MSC-sEVs. Notably, miRNA sequencing revealed that MSC-sEVs are enriched in multiple miRNAs that have been previously reported to target EMT-associated signaling pathways, suggesting a potential miRNA-mediated mechanism.</p><p><strong>Conclusion: </strong>Our study found that MSC-sEVs can effectively reverse renal EMT in HN, thereby promoting the restoration of renal function, revealing a possible mechanism by which MSC-sEVs treatment in renal fibrosis associated with HN. Taken together, this study provides a foundation for innovative therapeutic approaches and advanced pharmacological strategies for HN.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196682","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":"Early BMP7 Exposure Enhances Brown Adipogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells.","authors":"Sunmin Park, Ha Yeong Kim, Da Yeong Kim, Mirim Kim, Han Su Kim","doi":"10.1007/s13770-026-00850-0","DOIUrl":"https://doi.org/10.1007/s13770-026-00850-0","url":null,"abstract":"<p><strong>Background: </strong>Brown adipose tissue (BAT) dissipates energy via non-shivering thermogenesis, making it a promising therapeutic target for metabolic diseases. However, effective strategies for directing human stem cells toward brown adipocyte lineage remain to be fully established. Here, as an early commitment modulation study, we investigated whether stage-specific exposure to bone morphogenetic protein 7 (BMP7) during initial induction enhances brown adipocyte-like features and β-adrenergic responsiveness in tonsil-derived mesenchymal stem cells (TMSCs).</p><p><strong>Methods: </strong>TMSCs were induced to differentiate into white adipocyte-like cells (WA) or brown adipocyte-like cells using a two-step protocol. Among the brown adipogenic groups, BMP7 (50 ng/mL) was additionally administered during the early commitment stage (step 1) in one group (BA + BMP7) but not the other (BA), while both groups received BMP7 throughout the subsequent step 2 induction, allowing the stage-specific effect of early BMP7 priming to be evaluated. Lineage commitment and brown adipocyte-like features were assessed via Oil Red O staining, qPCR, western blotting, MitoTracker staining, and cAMP responsiveness upon β-adrenergic stimulation (isoproterenol).</p><p><strong>Results: </strong>Early BMP7 priming during the initial commitment stage effectively promoted brown adipocyte lineage commitment. Compared with the WA and BA group, BA+BMP7 cells exhibited significantly increased UCP1 protein expression, along with non-significant upward trends in ZIC1 and PGC1α, and a significant increase in the progenitor commitment marker Myf5. Furthermore, brown adipogenic differentiation significantly increased mitochondrial mass, showing an additional upward trend in the early BMP7-primed group, whereas β-adrenergic functional responsiveness distinguished the two brown adipogenic groups: upon isoproterenol stimulation, BA + BMP7 cells exhibited an increase in intracellular cAMP accumulation relative to their own basal state, alongside enhanced HSL phosphorylation, a pattern not observed to the same extent in brown-differentiated cells without early BMP7 priming.</p><p><strong>Conclusion: </strong>This early commitment modulation study demonstrates that temporal BMP7 exposure enhances brown adipocyte-like features and adrenergic sensitivity in TMSCs. Early stage-specific signaling modulation provides a viable strategy for directing stem cell lineage commitment toward brown adipocyte-like phenotypes for metabolic research.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171107","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":"Comparative Study of Mesenchymal Stem Cell Identity and Chondrogenic Differentiation Capacity of Human Nucleus Pulposus, Adipose and Bone Marrow Tissues Derived Mesenchymal Stem Cells.","authors":"Hataiwan Kunkanjanawan, Tanut Kunkanjanawan, Veerapol Khemarangsan, Siravich Suvithayasiri, Tawit Suriyo, Jutamaad Satayavivad, Warayos Trathitephun","doi":"10.1007/s13770-026-00824-2","DOIUrl":"10.1007/s13770-026-00824-2","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are multipotent mesoderm-derived cells with high proliferation capacity, self-renewal, paracrine activity, and multilineage differentiation potential. Autologous MSCs from the same patients are particularly valuable for regenerative therapies, including those targeting degenerative intervertebral disc disorder (DIVDD).</p><p><strong>Methods: </strong>In this study, we directly compared autologous MSC sources obtained from the same patients, thereby reducing biological variability and strengthening translational relevance. We compared MSCs isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and nucleus pulposus (NP-MSCs) obtained from the same DIVDD patient donor (N = 10 donors). We assessed their morphologies, proliferation abilities, immunophenotype, multilineage differentiation capacity, and chondrogenic differentiation-related gene and protein expression.</p><p><strong>Results: </strong>All three MSC populations displayed similar fibroblast-like morphology and consistent immunophenotypic profiles. However, their functional properties differed: AD-MSCs exhibited significantly higher proliferative activity and greater adipogenic differentiation potential (p < 0.01 and p < 0.001), while osteogenic and chondrogenic differentiation capacities were comparable across BM-MSCs, AD-MSCs, and NP-MSCs at both gene and protein levels (SOX9 and COMP).</p><p><strong>Conclusion: </strong>These findings suggest that AD-MSCs offer practical advantages in terms of proliferation capacity and accessibility. However, chondrogenic differentiation capacity was largely comparable across MSC sources. Further mechanistic studies and in vivo validation are required to determine their relative therapeutic efficacy for intervertebral disc regeneration.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1075-1088"},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550443","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":"Preclinical and Clinical Translation of Immunomodulatory Role of Mesenchymal Stem Cells in Cancer Therapy Era.","authors":"Yutao Wu","doi":"10.1007/s13770-026-00830-4","DOIUrl":"10.1007/s13770-026-00830-4","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are multipotent stromal cells with dual regenerative and immunomodulatory properties that have attracted growing attention in cancer therapy. Their inherent tumor-homing ability enables localized delivery of therapeutic agents, while their capacity to regulate both innate and adaptive immunity positions MSCs at the interface of stromal biology and cancer immunotherapy. However, MSC functions are highly context-dependent and vary across tumor types.</p><p><strong>Methods: </strong>This review summarizes preclinical and clinical evidence on the immunomodulatory roles of MSCs in cancer. Experimental studies and early-phase clinical trials involving unmodified, preconditioned, and genetically engineered MSCs, as well as MSC-derived extracellular vesicles, were evaluated.</p><p><strong>Results: </strong>Unmodified MSCs often promote immune evasion by expanding regulatory T cells, expressing checkpoint ligands, and secreting immunosuppressive and metabolic mediators, such as IDO, nitric oxide, and PGE₂. In contrast, engineered or primed MSCs can redirect immune responses toward activation, enhancing NK- and T-cell cytotoxicity and enabling targeted delivery of cytokines, oncolytic viruses, and pro-apoptotic ligands. Early clinical trials generally demonstrate safety and feasibility; however, efficacy remains variable due to heterogeneity of MSC sources, manufacturing challenges, and lack of standardized potency assays. Notably, tumor-promoting effects have been reported under specific conditions.</p><p><strong>Conclusion: </strong>MSCs Represent a highly plastic and programmable platform for immune modulation in cancer. Advances in genetic engineering and extracellular vesicle-based strategies may improve therapeutic efficacy while reducing oncogenic risk.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"989-1026"},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761896","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":"Application of Fibronectin-Coated Microparticles for Isolation of Human iPSC-Derived MSCs.","authors":"Jae Hyeok Jang, In Sun Hwang, Ji Seob Kim, Sunjun Lee, Min Hee Moon, Bowon Kim, Seo Jeong Kim, Jongho Choi, Young Her, Soo-Hong Lee, Byung-Hyun Cha","doi":"10.1007/s13770-026-00822-4","DOIUrl":"10.1007/s13770-026-00822-4","url":null,"abstract":"<p><strong>Background: </strong>Bone marrow-derived MSCs (BMMSCs) are limited by availability, donor variability, and age-related decline, highlighting the need for alternative MSC sources. Induced pluripotent stem cells (iPSCs) offer a scalable solution. This study introduces a novel three-dimensional culture platform based on fibronectin (FN)-coated microparticles to efficiently derive and expand human iPSC-derived MSCs (iMSCs).</p><p><strong>Methods: </strong>The system utilizes FN-coated non-porous (CytoDex) and porous (CytoPore) microparticles. FN coating efficacy on microparticle was confirmed using Rhodamine-labeled FN and confocal microscope. Base on various molecular cell biological experiment, the utilization of FN-coated CytoDex and CytoPore leverages an expanded surface area to improve iMSCs isolation. The characteristics and cell behaviors of iMSCs generated from FN-coated CytoDex and CytoPore was evaluated by immunophenotype analysis, cell proliferation, and senescence related assays. In vivo tissue regeneration was evaluated by microcomputed tomography and histopathological analyses.</p><p><strong>Results: </strong>The porous microparticle CytoPore significantly enhanced FN coating efficiency, cell attachment, and proliferation compared to CytoDex. FN-coated CytoPore enabled the selective isolation of a high-purity MSC population from spontaneously differentiated iPSCs (SD-iPSCs) by day 7, confirmed by distinct morphology and mesodermal marker expression. The resulting iMSCs exhibited immunophenotypic characteristics comparable to adult MSCs, along with superior proliferative capacity, extended telomere length, and minimal senescence over 10 passages, in contrast to BMMSCs. Furthermore, iMSCs demonstrated effective in vivo tissue regeneration in an osteochondral defect model.</p><p><strong>Conclusion: </strong>This novel FN-coated microparticle-based 3D culture platform enables efficient, large-scale production of high-quality iMSCs and holds strong potential for clinical applications in stem cell therapeutics and regenerative medicine.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1027-1040"},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798176","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":"Electrical Stimulation-Induced Modulation of Small Extracellular Vesicles in Regenerative Therapy.","authors":"Jae Hoon Kim, Jeong-Kee Yoon","doi":"10.1007/s13770-026-00828-y","DOIUrl":"10.1007/s13770-026-00828-y","url":null,"abstract":"<p><strong>Background: </strong>Small extracellular vesicles (sEVs) are nanoscale, membrane-bound vesicles mediating intercellular communication by transferring bioactive molecules, including nucleic acids, proteins, lipids, and metabolites. Electrical stimulation (ES) has emerged as a bioengineering strategy for modulating cellular electrophysiology, calcium signaling, and vesicle secretion. Although ES is increasingly recognized as a regulator of sEV biology, its effects on sEV biogenesis, cargo composition, and regenerative function have not been systematically defined. Therefore, this review aims to synthesize current evidence to clarify the influence of ES on sEV biogenesis, release, cargo remodeling, and functional outcomes in regenerative contexts.</p><p><strong>Methods: </strong>Relevant published literature was reviewed to summarize current evidence on the effects of electrical stimulation on sEV biogenesis, secretion, cargo composition, and regenerative function. Articles were selected based on their relevance to ES-mediated sEV regulation, electrically responsive tissues, and regenerative medicine applications.</p><p><strong>Results: </strong>The reviewed studies indicate that ES can regulate sEV secretion and alter molecular cargo profiles in a context-dependent manner. Evidence from diverse electroresponsive tissue-related systems suggests that ES-modulated sEVs may contribute to regenerative and tissue-protective responses.</p><p><strong>Conclusions: </strong>This review summarizes current evidence on ES-mediated sEV modulation across electroresponsive tissues. Given remaining challenges in standardization and in vivo mechanistic validation, we propose future directions including advanced EV tracking and cell-type-specific analyses. Overall, ES-enabled sEV modulation represents a promising strategy for next-generation regenerative therapies.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"949-973"},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148449760","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":"Vectors Trgeting Hepatocyte: Reconstructive Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes.","authors":"Yan-Feng Yin, Chun-Tao Yan, Zheng Guan, Lu Yu, Chun-Mei Lei, Dongdong Wang, Jiayin Yang","doi":"10.1007/s13770-026-00826-0","DOIUrl":"10.1007/s13770-026-00826-0","url":null,"abstract":"<p><strong>Background: </strong>Specific binding of the hepatitis B virus (HBV) pre-S1 protein to Na⁺/taurocholate Cotransporting Polypeptide (NTCP) on the surface of hepatocytes mediates viral entry into host cells. Exosomes, which serve as natural delivery vehicles, can protect their cargo from degradation in the extracellular environment.</p><p><strong>Methods: </strong>Umbilical cord mesenchymal stem cell (UC-MSC)-derived exosomes were isolated and characterized. The gene sequence encoding the CD90 C-terminal signal peptide was fused with the pre-S1 gene and cloned into a lentiviral vector (VP045-U6-PGK-preS1-CD90-hygro), enabling membrane anchoring of pre-S1 on UC-MSC-derived exosomes. PKH26 probe, Phalloidin-AF488 probe, and DiR dye were used to explore the targeting of reconstituted UC-MSC-derived exosomes on hepatocytes and liver.</p><p><strong>Results: </strong>Isolated UC-MSCs exhibited fibroblast-like morphology and retained the capacity to differentiate into osteoblasts, adipocytes, and chondrocyte. The immunophenotype of UC-MSCs was characterized as CD34^-CD45^-CD44⁺CD73⁺CD90⁺CD105⁺Oct-4⁺. UC-MSC-derived exosomes exhibited a cup-shaped bilayer structure, with a diameter of 78.47 ± 13.46 nm and a concentration of 1.28 × 10¹⁰ particles/mL. The VP045-U6-PGK-preS1-CD90-hygro lentivirus successfully mediated pre-S1 expression on the membranes of UC-MSC-derived exosomes. In vitro, hepatocytes (HepG2.2.15 and HepaRG cells) internalized significantly greater amounts of reconstituted UC-MSC-derived exosomes than native exosomes, with the effect being particularly pronounced in HepG2.2.15 cells. No significant difference was observed in lung cells. In vivo, reconstituted UC-MSC-derived exosomes were predominantly accumulated in the liver of BALB/c mice, whereas minimal signals were detected in the lung, spleen and kidney.</p><p><strong>Conclusion: </strong>UC-MSC-derived exosomes expressing pre-S1 exhibit specific tropism for hepatocytes and liver tissue. These engineered exosomes represent a promising delivery platform for therapeutic drugs and nucleic acid cargos in HBV-targeted therapy.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1089-1100"},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945747","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":"Potentiated Maturation of hPSC-Derived Dopaminergic Neurons via Convergent Genetic and Small Molecule Modulation.","authors":"Sanghyun Park, Dongyun Kim, Seo Hyun Yoo, Gyu-Bum Yeon, Jaewook Lee, Myung Soo Cho, Dong-Wook Kim, Dae-Sung Kim","doi":"10.1007/s13770-026-00820-6","DOIUrl":"10.1007/s13770-026-00820-6","url":null,"abstract":"<p><strong>Background: </strong>Ventral midbrain dopaminergic (vmDA) neurons derived from human pluripotent stem cells provide a powerful platform for modeling Parkinson's disease (PD) and developing therapeutic strategies. Although robust protocols exist for generating vmDA progenitors, maturation into functionally competent neurons typically requires prolonged culture periods and occurs with substantial heterogeneity in maturity, representing major bottlenecks.</p><p><strong>Methods: </strong>Building on established protocols for vmDA progenitor differentiation, we introduce a sequential strategy that specifically targets the subsequent phases of neuronal conversion and postmitotic maturation. Transient overexpression of the proneural transcription factor achaete-scute family bHLH transcription factor 1 (ASCL1) was applied to human embryonic stem cell-derived vmDA progenitors to induce neuronal commitment, followed by accelerated postmitotic maturation using the small-molecule cocktail GENtoniK. This approach was evaluated in CRISPR/Cas9-engineered human induced pluripotent stem cell (hiPSC) lines lacking either PINK1 or PRKN and their isogenic control hiPSCs.</p><p><strong>Results: </strong>Transient ASCL1 overexpression promoted rapid cell cycle exit and neuronal conversion of vmDA progenitors while preserving ventral midbrain identity and dopaminergic fate. Subsequent GENtoniK treatment enhanced postmitotic dopaminergic maturation and increased neurite complexity, synaptic organization, and dopaminergic neurotransmission without altering lineage specification. Consequently, within two weeks, our protocol yielded high-purity vmDA neurons with enhanced functional maturation from vmDA progenitors. Importantly, PINK1- and PRKN-deficient neurons generated from CRISPR/Cas9-engineered hiPSC lines using this strategy recapitulated key PD-associated mitochondrial phenotypes, including impaired mitophagy, mitochondrial dysfunction, and elevated oxidative stress.</p><p><strong>Conclusion: </strong>Taken together, these findings address the central limitations of current dopaminergic differentiation paradigms by enabling the rapid and uniform acquisition of advanced functional maturity, thereby providing a robust platform for disease modeling and translational research in PD.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1061-1074"},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346382","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":"Cell-Free Adipose Liquid Extract Combined with Vascularized Lymph Node Transfer for Treating Lymphedema: Implications for Human Therapy.","authors":"Lingli Jiang, Sanhong Yang, Fang Zhang, Fang Qi, Wenjie Pan, Anna Chiarini, Ilaria Dal Prà, Ubaldo Armato, Daniele De Santis, Hai Li, Shune Xiao, Chengliang Deng","doi":"10.1007/s13770-026-00829-x","DOIUrl":"10.1007/s13770-026-00829-x","url":null,"abstract":"<p><strong>Background: </strong>To evaluate whether the application of cell-free adipose liquid extract (ALE) synergistically enhances the therapeutic efficacy of vascularized lymph node transfer (VLNT) by reconstructing the lymphatic-vascular network and restoring the lymph node immune niche in a rat lymphedema model.</p><p><strong>Methods: </strong>A rat hindlimb lymphedema model was established involving popliteal lymph node excision. Animals were randomized into four groups: Control, ALE only, VLNT only, and VLNT combined with ALE (VLNT + ALE). ALE was prepared using a mechanical emulsification and filtration protocol. Edema resolution was monitored by limb circumference. Lymphatic drainage function was visualized via indocyanine green (ICG) lymphography. Histological assessments included Masson's trichrome and immunofluorescence for LYVE-1 (lymphangiogenesis), CD31 (angiogenesis), and MECA-79 (high endothelial venules, HEVs) to evaluate structural and functional regeneration.</p><p><strong>Results: </strong>The VLNT + ALE group achieved the most rapid and significant edema regression compared to VLNT or ALE alone. ICG lymphography revealed that the combined therapy orchestrated the formation of continuous, linear lymphatic channels, effectively eliminating dermal backflow. Histologically, ALE treatment significantly increased the density of both LYVE-1⁺ lymphatic vessels and CD31⁺ blood vessels, suggesting a dual-regenerative effect on the microenvironment. ALE directly promoted tube formation in human lymphatic endothelial cells (HLECs), confirming its pro-lymphangiogenic activity in vitro. Crucially, within the transplanted lymph nodes, ALE treatment restored the expression of MECA-79⁺ HEVs to levels comparable to healthy young nodes. This indicates that ALE not only supports graft survival but also preserves the essential lymphoid microarchitecture required for immune surveillance.</p><p><strong>Conclusions: </strong>Cell-free ALE synergistically enhances the therapeutic efficacy of VLNT by promoting vascular-lymphatic coupling and restoring the functional immune niche of transplanted nodes. As a readily available, safe, and cell-free biologic adjuvant, ALE represents a promising translational strategy to optimize surgical outcomes in secondary lymphedema.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1101-1114"},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536360","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":"L-Ascorbic Acid 2-Phosphate-Releasing Poly(trimethylene carbonate) Increases Cell Proliferation and Collagen Production: A Novel Material for Pelvic Organ Prolapse Tissue Engineering.","authors":"Katri Ala-Mononen, Dirk Grijpma, Alexander Efimov, Saana Mustakoski, Kirsi Kuismanen, Susanna Miettinen, Reetta Sartoneva","doi":"10.1007/s13770-026-00831-3","DOIUrl":"10.1007/s13770-026-00831-3","url":null,"abstract":"<p><strong>Background: </strong>Pelvic organ prolapse (POP) occurs due to the weakening of the pelvic floor connective tissues and their decreased collagen content, leading to the descent of pelvic organs into or through vagina. Therefore, biodegradable materials designed to enhance collagen production could be a future option for POP treatment.</p><p><strong>Methods: </strong>Here, we studied novel L-ascorbic acid 2-phosphate (A2P)-releasing biodegradable poly(trimethylene carbonate) (PTMC) materials. The effects of varying A2P concentrations (0, 5 or 10 wt%) were evaluated regarding material characteristics, such as component release and mechanical and surface properties. Further, materials' effect on proliferation, collagen production and attachment of human vaginal stromal cells (hVSCs) and human adipose-derived stromal cells (hASCs) were analyzed during 14-day culture period.</p><p><strong>Results: </strong>A2P-releasing PTMC had good handling characteristics and mechanical properties, such as high tensile and suture retention strength. Rapid, yet controlled release of A2P from the PTMC was observed in in vitro release studies. Our results demonstrate that A2P-releasing PTMC significantly increased the proliferation and total collagen content of both hVSCs and hASCs. Further, genetic expression of collagen types I (COL I) and III (COL III) significantly increased on A2P-releasing PTMC membranes, and extracellular COL I fibers were visible in cultures on PTMC5. Increased attachment and cell sheet formation were observed in both hVSC and hASC cultures on A2P-releasing PTMC, and A2P increased α-smooth muscle actin (α-SMA) expression in hASCs.</p><p><strong>Conclusion: </strong>Our results indicate that A2P-releasing PTMC is a promising option for enhancing tissue regeneration in applications for POP tissue engineering.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1041-1059"},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438170","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}