{"title":"Paxillin in mechanosensitive spatial control of lung endothelial cell regeneration.","authors":"Tadanori Mammoto, Priscilla Kyi, Mikaela Scheer, Tendai Hunyenyiwa, Elaheh Hashemi, Xiaolong Ma, Christopher E Turner, Chien-Wei Lin, Subramaniam Malarkannan, Akiko Mammoto","doi":"10.1038/s41536-026-00476-9","DOIUrl":"10.1038/s41536-026-00476-9","url":null,"abstract":"<p><p>Mechanical forces altered after unilateral pneumonectomy (PNX) control post-PNX lung growth. Here, we demonstrate that post-PNX endothelial regeneration is stimulated at the peripheral region of the mouse lung, requiring the focal adhesion (FA) protein, paxillin, while inhibition of mechanical tension attenuates the effects. Paxillin mediates stretching-induced YAP1-TEAD1 signaling, which stimulates GATA2 activity on angiogenic factor angiopoietin-2 (ANGPT2) transcription in endothelial cells (ECs), dictating post-PNX endothelial regeneration at the peripheral region. Deleting endothelial paxillin suppresses expression of GATA2 in the specific EC subtype, capillary type 1 ECs (CAP1s) following PNX. Extracellular matrix protein, collagen VI that impacts cell mechanical responses is expressed more at the peripheral region in the post-PNX mouse lungs, which drives paxillin expression, leading to EC regeneration. Mechanosensitive paxillin signaling in ECs mediates spatial control of post-PNX endothelial regeneration.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147977216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lauren G Porter, Mikayla S Jackson, Robert S Oakes
{"title":"Interventions and platforms that direct lymphangiogenesis to restore physiological homeostasis and enhance immunoregulation.","authors":"Lauren G Porter, Mikayla S Jackson, Robert S Oakes","doi":"10.1038/s41536-026-00472-z","DOIUrl":"10.1038/s41536-026-00472-z","url":null,"abstract":"<p><p>The lymphatic system maintains physiological homeostasis through constant immunosurveillance, immune cell trafficking, and regulation of interstitial fluid flow. Lymphatic dysfunction is associated with a wide range of pathologies, including cancer metastasis and lymphedema. Aberrant lymphatic structure also contributes to chronic wounds and transplanted organ rejection. These functional and structural deficits have inspired strategies for lymphatic vasculature modulation and tissue engineering to regulate immune functions during disease and injury rehabilitation. Lymphangiogenesis-the process of lymphatic vessel growth- is central to the success of these strategies and has broad potential if harnessed for therapeutic intervention and tissue integration. Here we review the opportunities and obstacles for biomolecular pathway modulation, nanotechnology, and tissue engineering to promote or inhibit lymphangiogenesis.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147935334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cold atmospheric plasma ameliorating skin barrier in chronic kidney disease.","authors":"Meng Wang, Hongli Jiang, Dingxin Liu, Wuying Xu, Lei Chen, Zifeng Wang, Hua Liu, Xue Zhao, Siyue Zhai","doi":"10.1038/s41536-026-00478-7","DOIUrl":"10.1038/s41536-026-00478-7","url":null,"abstract":"<p><p>Chronic kidney disease (CKD)-associated skin complications, including pruritus and xerosis, remain clinically challenging due to poorly understood pathological mechanisms. We utilized human skin tissues, adenine-induced CKD mice, and HaCaT cells to evaluate CAP interventions, including direct irradiation and topical application of CAP-activated hydrogel, on epidermal barrier function. Both CKD patients and mice exhibited significant barrier impairment, characterized by suppressed markers of proliferation (PCNA), differentiation (CK1), cornified envelope (filaggrin, loricrin), and tight junctions (claudin-1). CAP treatment effectively reversed these abnormalities, restoring the keratinocyte proliferation/differentiation balance, promoting terminal differentiation, and reducing transepidermal water loss. Mechanistically, CAP coordinated epidermal homeostasis by activating the β-catenin/YAP1 pathway (promoting regeneration) while concurrently inhibiting PI3K/AKT signaling (facilitating differentiation). CAP effectively restores the molecular machinery required for skin barrier integrity in CKD, alleviating associated dermatopathology. These findings establish a scientific basis for CAP as a non-invasive therapy for CKD-related skin complications.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147935315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The SHEDs-derived apoptotic bodies for inflammatory regulation in spinal cord repair.","authors":"Lihua Luo, Na Dong, Junpeng Xu, Chen Zhang, Sa Bao, Haichao Xu, Xiping Wang, Peng Dai, Caiyan Li, Qiao Zhang, Yibo Ying, Dawei Jiang, Shengcun Li, Ping Wu, Liqing Mei, Xiaokun Li, Junjie Deng, Yihuai Pan, Zhouguang Wang","doi":"10.1038/s41536-026-00475-w","DOIUrl":"10.1038/s41536-026-00475-w","url":null,"abstract":"<p><p>Neuroinflammation is a key therapeutic target for spinal cord injury (SCI). Apoptotic bodies (ABs) derived from mesenchymal stem cells may modulate early inflammation, promoting SCI repair. Stem cells from human exfoliated deciduous teeth (SHEDs), with neural crest origins, are promising for neurological therapies, but their ABs' role in SCI remains unclear. In this study, as exploratory research, we aimed to investigate the preliminary effects and mechanisms of SHEDs-derived ABs on the treatment of SCI. Herein, SHEDs-derived ABs enhanced functional recovery in SCI mice, improving BMS scores, joint movement, and bioelectrical conduction. Histologically, ABs boosted axonal growth and neuronal regeneration. Moreover, SHEDs-derived ABs significantly suppressed M1 polarization while enhancing M2 polarization in both in vitro and in vivo models. GO/KEGG analyses revealed AB enrichment in immune-related pathways. Mechanistically, the ANXA1/FPR2 axis was critical for ABs-induced microglia/macrophage polarization, with M1 regulation mediated by the NF-κB pathway and M2 modulation driven by the AKT/mTOR pathway. Thus, SHEDs-derived ABs may serve as a clinically translatable strategy for treating SCI by mediating immunomodulation via the ANXA1/FPR2 axis.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13316036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manuella M Godoi, Caroline Portela Peruzzi, Joao Vitor Alves Hoepers, Ana Merian da Silva, Henrique Sant'Ana Koepp do Nascimento, Felipe Nascimento Mateus, Ana Caroline Gonçalves, Guilherme Colla, Janice Koepp, Juliano Ferreira
{"title":"A modified bacterial nanocellulose-based advanced therapy product accelerates third-degree burn healing in murine models.","authors":"Manuella M Godoi, Caroline Portela Peruzzi, Joao Vitor Alves Hoepers, Ana Merian da Silva, Henrique Sant'Ana Koepp do Nascimento, Felipe Nascimento Mateus, Ana Caroline Gonçalves, Guilherme Colla, Janice Koepp, Juliano Ferreira","doi":"10.1038/s41536-026-00470-1","DOIUrl":"10.1038/s41536-026-00470-1","url":null,"abstract":"<p><p>Severe burn injuries represent a major global healthcare burden, with high costs and prolonged hospitalizations. Current treatments, including autologous skin grafting, are limited by donor availability, while allografts carry risks of immune rejection. Advanced Therapy Medicinal Products (ATMPs) offer a promising alternative for skin substitution. We evaluated the efficacy of ARTSkin, an alginate-modified bacterial nanocellulose-based ATMP, in a murine model of third-degree burns. ARTSkin was manufactured under good manufacturing practice (GMP) conditions in two formulations: an acellular scaffold and a cellular construct containing human dermal fibroblasts. The acellular formulation was first assessed in vitro for cytotoxicity and wound-healing capacity using a scratch assay. In vivo, acellular and cellular ARTSkin were evaluated in immunocompetent and immunosuppressed mice, respectively. Acellular ARTSkin was non-cytotoxic and enhanced fibroblast migration and proliferation in vitro. Both formulations significantly improved wound healing in vivo, with accelerated closure and reduced bleeding, hyperemia, edema, and crust formation. Transcriptomic analysis showed that cellular ARTSkin modulated genes involved in the proliferative phase of healing by preventing burn-induced dysregulation of Rac1, Vegfa, and Itga4, and downregulating the profibrotic gene Ctgf. These findings support ARTSkin as a promising skin substitute for burn therapy.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kathy Jacyniak, Catherine J A Williams, Hugues Beaufrère, Jeremy Simpson, Guo N Huang, Xiaoxin Chen, Matthew K Vickaryous
{"title":"Heart ventricle regeneration in the lizard Eublepharis macularius, the leopard gecko.","authors":"Kathy Jacyniak, Catherine J A Williams, Hugues Beaufrère, Jeremy Simpson, Guo N Huang, Xiaoxin Chen, Matthew K Vickaryous","doi":"10.1038/s41536-026-00469-8","DOIUrl":"10.1038/s41536-026-00469-8","url":null,"abstract":"<p><p>Among mammals, injury to the heart typically results in scar formation and diminished cardiovascular function. In contrast, some teleost fish and salamanders can replace damaged heart tissue and restore overall function. For most species, however, less is known. Here, we investigate cardiac self-repair in an amniote capable of multi-tissue regeneration, the leopard gecko (Eublepharis macularius). To create a heart lesion, we placed a liquid nitrogen-cooled metal probe directly onto the ventricle. The result was a cryoinjury to ~20% of the ventricle. Cardiac cryoinjury induced localized cardiac cell death, followed by an increase in cell proliferation by injury-adjacent cardiomyocytes and non-cardiomyocytes. By 100 days, the histology of the ventricular myocardium was nearly completely restored. Echocardiography and invasive hemodynamic monitoring demonstrated that global cardiac function is restored within this timeframe, verifying functional replacement of the myocardium. To explore the molecular basis, we performed bulk RNA sequencing of the injury-adjacent tissue and found that many of the molecular mechanisms common to other cardiac regenerating species, including genes involved in heart development, glycolysis, and extracellular matrix deposition, are also conserved in geckos. Taken together, this work expands the comparative framework of heart regeneration to include reptiles and indicates that the ability to replace missing or damaged cardiomyocytes is shared across >50 million years of evolution.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13190692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kunal Bhanot, Neal Thurley, Robin O Cleveland, Jolet Mimpen, Sarah J B Snelling, Rory Rickard, Robert Staruch
{"title":"Three-dimensional models of skeletal muscle under tension: a systematic review and core outcome set.","authors":"Kunal Bhanot, Neal Thurley, Robin O Cleveland, Jolet Mimpen, Sarah J B Snelling, Rory Rickard, Robert Staruch","doi":"10.1038/s41536-026-00464-z","DOIUrl":"10.1038/s41536-026-00464-z","url":null,"abstract":"<p><p>Biologically representative three-dimensional (3D) skeletal muscle models are required to understand the mechanisms underpinning muscle disease. The primary aim of this systematic review is to evaluate the current literature on 3D skeletal muscle models under tension. Its secondary aim is to explore injury mechanisms and generate a novel Core Outcome Set (COS) for reporting of such models. In vitro studies that utilised any skeletal muscle cell types cultured with an anchor system imposing axial strain were eligible for inclusion. A modified Delphi approach using corresponding authors of included studies was then developed to obtain a COS. This systematic review was reported in compliance with the PRISMA 2020 checklist. 37 articles were included. Of these, 7 articles induced an injury in their model. Cell lines used were both human and animal. Immunohistochemical testing on models revealed greatest concordance for myosin heavy chain (MHC), alpha actinin, and Pax7 as a means of demonstrating striated muscle. The final COS agreed on multiple reporting criteria for the validation of models based on morphology, phenotype and function. This systematic review summarises the current literature and has developed core outcome reporting for models of 3D skeletal muscle that impose axial strain.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13269917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Palmieri, Giorgia Bimbi, Maxime Ferrand, Matteo Marcello, Louna Pili, Ai Vu Hong, Abbass Jaber, Riyad El-Khoury, Guy Brochier, Anne Bigot, David Israeli, Isabelle Richard, Sonia Albini
{"title":"Author Correction: Disease exacerbation in human DMD MYOrganoids enables gene therapy evaluation and unveils persistence of fibrotic activity.","authors":"Laura Palmieri, Giorgia Bimbi, Maxime Ferrand, Matteo Marcello, Louna Pili, Ai Vu Hong, Abbass Jaber, Riyad El-Khoury, Guy Brochier, Anne Bigot, David Israeli, Isabelle Richard, Sonia Albini","doi":"10.1038/s41536-026-00474-x","DOIUrl":"10.1038/s41536-026-00474-x","url":null,"abstract":"","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"11 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tatsuya Ogawa, Min Chen, Soung-Hoon Lee, Denise L Gay, Mayumi Ito
{"title":"Dissecting the boundary of quiescence and activation of murine melanocyte stem cells in the hair follicle niche.","authors":"Tatsuya Ogawa, Min Chen, Soung-Hoon Lee, Denise L Gay, Mayumi Ito","doi":"10.1038/s41536-026-00460-3","DOIUrl":"10.1038/s41536-026-00460-3","url":null,"abstract":"<p><p>Melanocyte stem cells (McSCs) are a crucial melanocyte reservoir within the hair follicle niche. This review provides an overview of the processes for McSC quiescence and activation. Because McSCs closely interact with hair follicle stem cells, we have focused on this interaction. Given the high prevalence of hair graying, the McSC system serves as a model for cellular aging. Here, we highlight current research on the mechanisms of hair graying.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147617073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriel Garnik Hovhannisyan, Tawba Akhourbi, Sema Elif Eski, Isabelle Pirson, Esteban N Gurzov, Sumeet Pal Singh
{"title":"CellCousin2: an optimized system for partial ablation and tracing of regenerative lineages.","authors":"Gabriel Garnik Hovhannisyan, Tawba Akhourbi, Sema Elif Eski, Isabelle Pirson, Esteban N Gurzov, Sumeet Pal Singh","doi":"10.1038/s41536-026-00473-y","DOIUrl":"10.1038/s41536-026-00473-y","url":null,"abstract":"<p><p>Regeneration can rely on multiple cellular sources, including stem cells, self-duplicating cells, and transdifferentiating cells. A central question in regenerative biology is how these distinct lineages contribute to repair and interact within a functionally regenerated tissue. We previously developed the CellCousin system to study cellular plasticity using inducible recombination and nitroreductase-mediated ablation in zebrafish. Here, we present CellCousin2, which introduces two key improvements for the long-term tracking of spared and regenerating cells. First, to reduce background recombination, we developed a Dihydrofolate Reductase (DHFR)-CreER system with dual control: DHFR-mediated degradation in the absence of trimethoprim, and tamoxifen-dependent activation. This combination minimizes leakiness while maintaining high recombination efficiency. Second, we replaced the original nitroreductase with NTR2.0, enabling effective ablation with a tenfold lower metronidazole concentration, reducing off-target effects on the liver. Together, these enhancements make CellCousin2 a robust platform for dissecting the dynamics and interactions of regenerative lineages.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}