Tissue engineering and regenerative medicine最新文献

{"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":5.1,"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":5.1,"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}

{"title":"High-Concentration Type I Atelocollagen Enhances Early Cartilage Regeneration: An In Vivo Comparative Study.","authors":"Bo Seung Bae, Seon Ae Kim, Eun Jeong Go, Jae Woong Jung, Mi-La Cho, Asode Ananthram Shetty, Seok Jung Kim","doi":"10.1007/s13770-025-00788-9","DOIUrl":"10.1007/s13770-025-00788-9","url":null,"abstract":"<p><strong>Background: </strong>Type I atelocollagen is used to treat full-thickness chondral lesions. However, evidence on the concentration-dependent effects of atelocollagen-based scaffolds on chondrogenesis is lacking. This study aimed to evaluate the in vitro and in vivo chondrogenic potentials of low-, intermediate-, and high-concentration atelocollagen-based scaffolds in a rabbit model of osteochondral defects.</p><p><strong>Methods: </strong>Human mesenchymal stem cells (hMSCs) were encapsulated in 3%, 6%, and 9% type I collagen gels to assess cell viability and chondrogenic differentiation in vitro. In vivo, full-thickness osteochondral defects (4 × 4 mm) were created in 24 rabbits and treated as follows: Group 1 (microfracture only), Group 2 (microfracture + 3% atelocollagen), Group 3 (microfracture + 6%), and Group 4 (microfracture + 9%). The animals were euthanized at 4, 8, or 12 weeks. Macroscopic and histological outcomes were evaluated using gross morphological assessment and modified O'Driscoll scores.</p><p><strong>Results: </strong>At 8 weeks postoperatively, Group 4 (7.17 ± 0.76) exhibited significantly higher macroscopic scores than Group 2 (3.83 ± 0.29, p < 0.001) and Group 3 (4.50 ± 0.50, p < 0.001), indicating near-complete defect filling and smooth surface restoration. At 12 weeks, Groups 2 (7.33 ± 0.58), 3 (7.50 ± 0.87), and 4 (8.00 ± 0.00) all demonstrated significantly higher macroscopic scores than Group 1 (0.17 ± 0.12, p < 0.001 for all). Histologically, all atelocollagen-treated groups (Group 2:20.77 ± 1.55; Group 3:23.5 ± 1.00; Group 4:23.67 ± 1.44) exhibited significantly higher scores than Group 1 (1.67 ± 0.29, p < 0.001), with Group 4 achieving the highest overall.</p><p><strong>Conclusion: </strong>High-concentration atelocollagen-based scaffolds significantly enhanced both the efficiency and quality of cartilage regeneration by providing mechanical support and a favorable microenvironment for chondrogenesis.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"475-490"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953048","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":"Therapeutic Effects of N-Acetylcysteine-Primed, Iron Oxide Nanoparticle-Enhanced Mesenchymal Stem Cell Exosomes in Ototoxicity Hearing Loss.","authors":"Temuulen Batsaikhan, Hyun Su Lee, Hyokyung Yang, Rumana Ferdushi, Jaehong Key, Young Joon Seo","doi":"10.1007/s13770-025-00784-z","DOIUrl":"10.1007/s13770-025-00784-z","url":null,"abstract":"<p><strong>Background: </strong>Sensorineural hearing loss caused by ototoxic agents remains irreversible due to the limited regenerative capacity of cochlear hair cells. Exosome-based therapies derived from mesenchymal stem cells (MSCs) offer a promising, cell-free alternative to protect auditory structures by modulating oxidative stress and inflammation. In this study, we evaluated the therapeutic potential of exosomes isolated from nanoparticle (NP) labeled, N-acetylcysteine primed tonsil-derived mesenchymal stem cells (T-MSCs), hereafter referred to as SPISOME-NAC, in kanamycin-induced ototoxicity models.</p><p><strong>Methods: </strong>T-MSCs were labeled with positively charged PLGA-PEI clustered SPIONs, with or without NAC pretreatment. Antioxidant enzyme activity (SOD, CAT, GSH), ROS levels, and PRDX1 expression were assessed in vitro. Exosomes were isolated and analyzed via nanoparticle tracking analysis. Their therapeutic efficacy was evaluated in both ex vivo cochlear explants and mouse model of kanamycin-induced ototoxicity. Hair cell survival was quantified via Myosin VIIa immunostaining, and auditory function was assessed using auditory brainstem responses (ABR). Pro-inflammatory cytokines (TNF-α, IL-1, IL-6) were measured via qRT-PCR.</p><p><strong>Results: </strong>NAC pretreatment significantly enhanced cell viability, increased GSH activity, and reduced intracellular ROS and PRDX1 levels in NP-labeled T-MSCs. Exosomes derived from NAC-pretreated cells (SPISOME-NAC) conferred superior protection to cochlear hair cells, particularly in the basal turn, and significantly improved hearing thresholds in vivo. Furthermore, SPISOME-NAC treatment downregulated inflammatory cytokines in cochlear tissue.</p><p><strong>Conclusion: </strong>SPISOME-NAC exhibit enhanced antioxidant and anti-inflammatory properties, providing functional protection in an ototoxicity-induced hearing loss model. By preventing ROS-mediated mitochondrial damage and apoptosis in cochlear hair cells, NAC interrupts a key pathogenic mechanism in ototoxicity, preserving auditory structure and function. These findings support NAC-primed exosomes as a novel therapeutic strategy for sensorineural hearing loss.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"367-379"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166818","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":"Umbilical Cord Mesenchymal Stem Cells and Wnt Pathway Modulation: A Novel Therapy for Liver Cirrhosis and Steatosis.","authors":"Yanxuan Wen, Nouman Amjad, Omar Mukamab, Obed Boadi Amissah, Wei Xie, Peng Zhou, Aishi Song, Lan Wang, Jiaxing Li, Rongqi Huang, Sihao Deng, Zhiyuan Li","doi":"10.1007/s13770-025-00780-3","DOIUrl":"10.1007/s13770-025-00780-3","url":null,"abstract":"<p><strong>Background: </strong>The Wnt signalling pathway, one of the key classical stem cell pathways, plays an important role in helping the liver regenerate after injury. Stem cells can influence changes in adult cell behaviour by either activating or inhibiting this pathway. When liver damage is severe, the organ's ability to regenerate may be compromised, sometimes leading to structural changes. Umbilical cord-derived mesenchymal stem cells have shown promise in improving the liver microenvironment more effectively through the classical Wnt pathway.</p><p><strong>Methods: </strong>Studies were conducted on both reviews and original experiments. This paper used a repeated-measures design, and statistical analysis was performed using a two-factor, two-level repeated-measures model to analyze the experimental results. The measurements taken before and after the intervention were compared, and interactions were examined. C57/6 BAL mice were randomly divided into two to three groups, with in vivo Choline-methionine deficiency C57 black mouse animal disease models, and hepG2 replace complex intake primary liver cell problem to mimic in vitro cell models simulated. One sample from each group was randomly selected for model validation, and stem cell injection experiments were conducted after validation. The experiments were carried out in a wholly randomized manner to explore the phenotype and intrinsic mechanisms of liver cirrhosis and steatosis.</p><p><strong>Results: </strong>In cirrhosis, inflammatory fibrosis, endoplasmic reticulum stress, and mitochondrial damage are key virulent factors in the primary stage. After treating mice for a month and a half, the AST content in the peripheral blood plasma of animals and the expression of ALT increased. The interventional treatment of umbilical cord mesenchymal cell infusion (three times a month at doses of 10⁵, 4 × 10⁵, or 10⁶) has further contributed to understanding the underlying mechanisms. The Wnt pathway plays a significant role in organ and tissue reversing function (p < 0.05).</p><p><strong>Conclusion: </strong>Umbilical cord mesenchymal stem cells were used to treat cirrhosis, ranging from end-stage to early stages, in methionine-deficient rats by modulating the Wnt pathway. It can inhibit the progression of steatosis-related inflammation and fibrosis, further depresses cirrhosis in mice and humans, and underscores the significance of umbilical stem cells in public health.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"439-461"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990675","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":"Combining Surface Modification and Bioactive Cues to Enhance Medpor® Implant Integration In Vivo.","authors":"Dina Gadalla, Maeve M Kennedy, Jamie E Ganem, Sriya Yeleswarapu, Amanda M Richards, Rachel M Wells, David G Lott","doi":"10.1007/s13770-025-00783-0","DOIUrl":"10.1007/s13770-025-00783-0","url":null,"abstract":"<p><strong>Background: </strong>Achieving stable and functional integration of synthetic implants with host tissue remains a key challenge in tissue engineering. Medpor®, a porous high-density polyethylene (HDPE) implant widely used in craniofacial reconstruction, provides excellent mechanical strength but lacks bioactivity, limiting early cell adhesion, vascularization, and extracellular matrix (ECM) deposition.</p><p><strong>Methods: </strong>To enhance Medpor® biointegration, we employed a multi-faceted modification strategy combining plasma treatment with biologically active components. Treated implants were coated with collagen and fibrin hydrogels and further supplemented with a platelet-derived Purified Exosome Product (PEP). Modified and control implants were evaluated in a subcutaneous mouse model to assess host tissue response, vascularization, and implant integration.</p><p><strong>Results: </strong>Tissue ingrowth was observed in the pores of all Medpor® implants. Plasma treatment significantly increased the surface hydrophilicity of Medpor®, promoting host cell adhesion and tissue infiltration. Implants modified with both hydrogels and PEP exhibited enhanced ECM deposition, greater vascular density, and improved tissue integration compared to untreated Medpor®. The combination of physicochemical surface treatment and biochemical cues led to a synergistic effect, supporting tissue ingrowth and angiogenesis under a controlled host immune response.</p><p><strong>Conclusion: </strong>This study demonstrates that integrating plasma surface modification with bioactive hydrogels and PEP can effectively enhance the biointegration of Medpor® implants in vivo. The combined approach significantly enhances implant vascularization and ECM development, offering a promising translational strategy for improving synthetic implant performance in regenerative and reconstructive biomaterial applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"463-474"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953016","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":"Therapeutic Efficacy of Mesenchymal Stem Cells (MSCs) on Alzheimer's Disease: Review of Clinical Results.","authors":"Ae-Lee Kim, Woon Kyu Lee, Soonjo Kwon, Inbo Han, Byung Hyune Choi","doi":"10.1007/s13770-025-00782-1","DOIUrl":"10.1007/s13770-025-00782-1","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) presents significant unmet medical needs with no effective therapeutic options. Current pharmacological treatments provide only symptomatic relief and do not prevent the ongoing neurodegeneration. Cell therapies using mesenchymal stem cells (MSCs) are being widely investigated for its potential in treating AD but remain unverified. This review aimed to evaluate therapeutic effects of MSCs on AD patients through a review of clinical trial literatures.</p><p><strong>Methods: </strong>Publications and registered clinical trials from January 2011 to June 2025 were collected from the international databases (ClinicalTrials.gov, PubMed, Web of Science, SCOPUS) using the keywords of \"Alzheimer's disease\", \"mesenchymal stem cells\", and \"clinical trials\". After initial screening and sorting, 17 clinical trials and 4 related papers were finally selected for in-depth analysis.</p><p><strong>Results: </strong>The 17 clinical trials were mostly early stages with 4 phase 1 (23.5%), 9 phases 1/2 (52.9%), 3 phase 2 (17.7%), and 1 pilot phase (5.9%). The source of MSCs included allogeneic umbilical cord blood (UCB) in 5 trials (29.4%), autologous adipose tissue in 4 (23.5%), allogeneic umbilical cord (UC) in 3 (17.6%), allogeneic bone marrow (BM) in 3 (17.6%), allogeneic placenta in 1 (5.9%) and 1 unknown (5.9%). Administration routes were primarily intravenous (IV) infusion in 12 trials (70.6%), intracerebroventricular (ICV) infusion via Ommaya reservoir in 3 (17.6%), and stereotactic brain injection (SBI) in 2 (11.8%). Among the 17 clinical trials, outcome data of 7 trials have been reported in 4 clinical papers and 1 clinical results posted in ClincalTrials.gov: 4 trials using UCB MSCs (NEUROSTEM-AD) in 2 papers, 2 trials using BM MSCs (Lomecel-B) in 2 papers and 1 trial using adipose MSCs (AstroStem) in ClinicalTrials.gov. All 5 reports using different cell types, administration routes or dosages claimed the safety of MSCs administration. As for the therapeutic efficacy, 2 reports using Lomecel-B reported meaningful improvement in AD pathophysiology or cognitive functions, while the other 3 reports using NEUROSTEM-AD or AstroStem failed to show statistically significant efficacy.</p><p><strong>Conclusion: </strong>The analysis of 17 clinical trials and 5 relevant clinical outcomes showed that MSCs therapy if feasible and generally safe in AD patients. There are indications of potential therapeutic benefits such as improved cognitive function or quality of life measures in some AD patients. However, its therapeutic efficacy has not been proven definitely due to small size of subjects, variations in dosage, MSCs source, and administration scheme (route, timing, and frequency). Larger subject sizes and well-controlled trials are needed to provide more conclusive evidence.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"343-365"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967123","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 Subcutaneous Derived Stromal Vascular Fraction Endothelial Cells Display Venous and Arterial Markers in Culture and 3D Capillaries.","authors":"Tobias Schwager, Nathalie A Senn, Roland Böni, Ueli Moehrlen, Agnes S Klar, Thomas Biedermann","doi":"10.1007/s13770-025-00790-1","DOIUrl":"10.1007/s13770-025-00790-1","url":null,"abstract":"<p><strong>Background: </strong>The Stromal Vascular Fraction (SVF) derived from human subcutaneous fat has attracted pivotal interest in clinical applications for its regenerative and anti-inflammatory properties. A deeper characterisation of the endothelial cells within the SVF, across both traditional and tissue-engineered culture systems, is essential for advancing our understanding of endothelial cell biology and enhancing regenerative medicine therapies, including skin substitutes.</p><p><strong>Methods: </strong>This study investigates endothelial cells from the SVF of human subcutaneous white adipose tissue in 2D culture and 3D bioengineered skin models to better define their specific subtypes. Immunofluorescence analysis was used to assess the SVF, with particular focus on endothelial cells, including their ability to form capillary-like networks within type I collagen hydrogels.</p><p><strong>Results: </strong>Analysis of the SVF-derived cells showed PLVAP-positive blood endothelial cells but no lymphatic endothelial cells. The blood endothelial cells could be discriminated into NR2F2- and CD62E-positive venous endothelial cells and NRP1-expressing arterial endothelial cells. Within the 3D hydrogels, the blood endothelial cells formed venous and arterial capillaries.</p><p><strong>Conclusion: </strong>We characterised endothelial cells from human subcutaneous SVF, identifying venous and arterial blood endothelial cells while confirming the absence of lymphatic endothelial cells in vitro. These findings underline that subcutaneous adipose tissue is an attractive cell source due to its ease of isolation and abundance of endothelial cells for skin tissue engineering and regenerative medicine in general.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"413-428"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158455","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":"Transcriptomic Profiling Reveals Mechanisms of Anoikis Resistance in Spheroid-Cultured Human Umbilical Cord Mesenchymal Stem Cells.","authors":"Yuma Iwata, Tomofumi Kodama, Takahiro Ishikawa, Li Ni, Xianqi Li, Koki Baba, Koyo Takahashi, Naoto Ogiwara, Sonoko Hatano, Akifumi Furuhashi, Yoshiaki Kazaoka, Hideaki Kagami","doi":"10.1007/s13770-025-00779-w","DOIUrl":"10.1007/s13770-025-00779-w","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem (stromal) cells are a promising cell source for regenerative medicine, but their therapeutic efficacy is often limited by poor engraftment and survival post-transplantation. One major contributing factor is anoikis, a form of apoptosis triggered by cell detachment from the extracellular matrix. Spheroid culture systems have shown potential to enhance cell survival and stemness, yet the mechanisms by which they confer resistance to anoikis remain unclear.</p><p><strong>Methods: </strong>We established spontaneous spheroids from human umbilical cord-derived mesenchymal stem (stromal) cells (UC-MSCs) and performed RNA-sequencing analysis to compare gene expression profiles between spheroid and monolayer cultures. Differentially expressed genes were identified and subjected to GO and pathway enrichment analyses. Functional assays included the use of PI3K/Akt and HIF-1 pathway inhibitors to dissect their role in anoikis regulation. Expression levels of apoptosis-related genes were validated by qRT-PCR.</p><p><strong>Results: </strong>Spheroid UC-MSCs exhibited significantly enhanced resistance to anoikis. Transcriptomic analysis revealed upregulation of both pro-apoptotic and anti-apoptotic genes, suggesting a balanced but regulated apoptotic threshold. Downregulation of executioner genes such as BAX, BAK1, and FADD, along with activation of PI3K/Akt and HIF-1α pathways, suggested effective suppression of apoptotic execution. Inhibitor experiments confirmed these pathways as key contributors to anoikis resistance.</p><p><strong>Conclusion: </strong>Our findings demonstrate that spheroid formation promotes a survival-permissive gene expression profile in UC-MSCs, driven in part by PI3K/Akt and hypoxia signaling. These insights advance the understanding of spheroid-mediated anoikis resistance and may inform strategies to enhance stem cell-based therapies.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"395-412"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012577","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":"Alkaline Phosphatase-Regulated C-C Motif Chemokine Ligand 5 (CCL5) Functions as a Critical Mediator of Hair Follicle Neogenesis.","authors":"Mi Hee Kwack, Myungsu Jung, Young Kwan Sung","doi":"10.1007/s13770-026-00792-7","DOIUrl":"10.1007/s13770-026-00792-7","url":null,"abstract":"<p><strong>Background: </strong>Alkaline phosphatase (ALP) is a well-established molecular marker of dermal papilla (DP) cells, and its activity closely correlates with their hair-inductive (trichogenic) capacity. This study aimed to identify downstream effectors regulated by ALP that contribute to trichogenicity, and to validate their functional significance in hair follicle neogenesis.</p><p><strong>Methods: </strong>A cytokine array was employed to screen ALP-dependent secreted factors in three-dimensional (3D) cultured human DP spheres. The expression of C-C motif chemokine ligand 5 (CCL5) and its receptor C-C chemokine receptor type 1 (CCR1) was confirmed by quantitative real-time PCR and immunohistochemistry in human hair follicles and murine skin. Functional roles of CCL5 in DP spheres and CCR1 in mouse epidermal cells were evaluated using siRNA-mediated knockdown followed by in vivo patch hair regeneration assays.</p><p><strong>Results: </strong>ALP knockdown significantly reduced CCL5 expression in DP spheres. Silencing of CCL5 in DP spheres markedly decreased their hair-inductive capacity, while CCR1 knockdown in epidermal cells impaired hair follicle formation. Combined knockdown of CCL5 in DP cells and CCR1 in epidermal cells completely abolished hair follicle neogenesis.</p><p><strong>Conclusion: </strong>These findings identify CCL5 as a critical downstream mediator of ALP-regulated trichogenicity in human DP spheres, with CCR1 serving as its essential receptor in epidermal cells. The ALP-CCL5-CCR1 axis represents a promising therapeutic target for promoting hair regeneration.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"429-437"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435688","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}