npj Regenerative Medicine最新文献_第7页

Cyclin A2 induces cytokinesis in human adult cardiomyocytes and drives reprogramming in mice. 细胞周期蛋白A2诱导人类成年心肌细胞的细胞分裂，并在小鼠中驱动重编程。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2025-11-03 DOI: 10.1038/s41536-025-00438-7

Esmaa Bouhamida, Sangeetha Vadakke-Madathil, Prabhu Mathiyalagan, Amaresh K Ranjan, Amir Khan, Cherrie D Sherman, Paul E Miller, Andre Ghetti, Najah Abi-Gerges, Hina W Chaudhry

{"title":"Cyclin A2 induces cytokinesis in human adult cardiomyocytes and drives reprogramming in mice.","authors":"Esmaa Bouhamida, Sangeetha Vadakke-Madathil, Prabhu Mathiyalagan, Amaresh K Ranjan, Amir Khan, Cherrie D Sherman, Paul E Miller, Andre Ghetti, Najah Abi-Gerges, Hina W Chaudhry","doi":"10.1038/s41536-025-00438-7","DOIUrl":"10.1038/s41536-025-00438-7","url":null,"abstract":"Cyclin A2 (CCNA2), a master cell cycle regulator silenced in postnatal cardiomyocytes, promotes cardiac repair in animal models. However, its effect on cytokinesis in adult human cardiomyocytes was previously unknown. We engineered a replication-deficient adenoviral vector encoding human CCNA2 under the cardiac Troponin T promoter and delivered it to freshly isolated cardiomyocytes from adult human hearts. Time-lapse live imaging revealed the induction of complete cytokinesis with preservation of sarcomeres and calcium mobilization in redifferentiated daughter cardiomyocytes. Single-nucleus transcriptomic profiling of CCNA2-transgenic and non-transgenic mouse hearts uncovered a cardiomyocyte subpopulation characterized by enrichment of cytokinesis, proliferation, and reprogramming gene signatures. Ultra-deep bulk RNA sequencing of adult and fetal human hearts further highlighted reprogramming pathways relevant to CCNA2-induced effects. Together, these findings demonstrate that CCNA2 can reinitiate cytokinesis in adult human cardiomyocytes, illuminating conserved molecular programs that support its promise as a regenerative gene therapy for the heart.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"47"},"PeriodicalIF":7.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12583628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440089","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}

引用次数: 0

Optical mapping of the interface between iPSC-derived grafts and swine myocardium suggests potential arrhythmia mechanisms. ipsc来源的移植物和猪心肌之间界面的光学定位提示潜在的心律失常机制。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2025-11-03 DOI: 10.1038/s41536-025-00434-x

Bijay Guragain, Hanyu Zhang, Yuhua Wei, Lei Ye, Gregory P Walcott, Jack M Rogers, Jianyi Zhang

{"title":"Optical mapping of the interface between iPSC-derived grafts and swine myocardium suggests potential arrhythmia mechanisms.","authors":"Bijay Guragain, Hanyu Zhang, Yuhua Wei, Lei Ye, Gregory P Walcott, Jack M Rogers, Jianyi Zhang","doi":"10.1038/s41536-025-00434-x","DOIUrl":"10.1038/s41536-025-00434-x","url":null,"abstract":"We used high-resolution optical mapping (~50 µm) to investigate potential arrhythmia mechanisms following transplantation of engineered cardiac tissue. We induced myocardial infarction in 6 immunosuppressed pigs and implanted cardiac spheroids into the border zone. One week later, 600-µm-thick cardiac slices containing implanted spheroids were harvested and electrical propagation was imaged. Histology showed low connexin-43 expression, scar, and misaligned muscle fibers at the graft-host interface. We observed propagation from host-to-graft in 10 slices from 3 pigs. Host-graft electrical bridges were spaced by millimeters. Propagation was ~4-fold slower in the graft than host. One graft beat spontaneously, but activation did not propagate from graft-to-host in this, or any other slice. We did not observe reentry, but slow in-graft conduction and sparse electrical bridges provided opportunity for reentry induction. These data reveal potential for reentrant or focal arrhythmias 1 week post-implant, which may resolve with maturation of the graft and the graft-host interface.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"50"},"PeriodicalIF":6.5,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12583502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439133","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}

引用次数: 0

An infusible extracellular matrix biomaterial improves survival in a model of severe systemic inflammation. 不溶性细胞外基质生物材料可提高严重全身性炎症模型的存活率。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2025-10-31 DOI: 10.1038/s41536-025-00435-w

Maria L Karkanitsa, Raymond M Wang, Anne C Lyons, Joshua M Mesfin, Alexander Chen, Martin T Spang, Filiberto Quintero, Kaitlyn Sadtler, Mark Hepokoski, Karen L Christman

{"title":"An infusible extracellular matrix biomaterial improves survival in a model of severe systemic inflammation.","authors":"Maria L Karkanitsa, Raymond M Wang, Anne C Lyons, Joshua M Mesfin, Alexander Chen, Martin T Spang, Filiberto Quintero, Kaitlyn Sadtler, Mark Hepokoski, Karen L Christman","doi":"10.1038/s41536-025-00435-w","DOIUrl":"10.1038/s41536-025-00435-w","url":null,"abstract":"Excess systemic inflammation can often be lethal in septic and trauma patients due to the onset of multiple organ dysfunction syndrome (MODS). As of right now, there are no effective immunomodulatory therapeutics that can promote survival within this patient population. Pro-regenerative extracellular matrix (ECM) biomaterials have shown success for the treatment of local inflammation but have not been fully explored for treating systemic inflammation. Here, we demonstrate the efficacy of an intravenously delivered infusible ECM (iECM) material, which promotes increased survival in a murine model of MODS by decreasing systemic mediators of inflammation. Lung and kidney failure are associated with higher mortality in MODS compared to other organ failures, and we demonstrate that iECM localizes primarily to kidney and lung tissues during systemic inflammation induced by endotoxin. iECM successfully lowered vascular permeability within lung tissue and lowered levels of inflammatory cytokine signaling, such as IL-6, verified via ELISA and gene expression analyses. We also demonstrated that immune cell infiltration into lung tissue was modulated with iECM treatment, with an increase in neutrophil retention in the lung and decreases in pro-inflammatory macrophage presence. In summation, iECM improves survival from severe systemic inflammation by decreasing the local and systemic inflammatory signaling pathways that contribute to MODS. These results provide a strong rationale for translational studies of iECM treatment in systemic inflammatory syndromes, including sepsis and trauma.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"48"},"PeriodicalIF":6.5,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12578793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423474","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}

引用次数: 0

Reversion of passaged nucleus pulposus cells to notochordal-type cells by FoxA2 upregulation. 通过上调FoxA2使传代髓核细胞向脊索型细胞转变。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2025-10-31 DOI: 10.1038/s41536-025-00437-8

Sajjad Ashraf, Aaryn Montgomery-Song, Campbell Thom, Evan Davison Kotler, Byron Chan, Alena Zelinka, Paul Santerre, Rita Kandel

{"title":"Reversion of passaged nucleus pulposus cells to notochordal-type cells by FoxA2 upregulation.","authors":"Sajjad Ashraf, Aaryn Montgomery-Song, Campbell Thom, Evan Davison Kotler, Byron Chan, Alena Zelinka, Paul Santerre, Rita Kandel","doi":"10.1038/s41536-025-00437-8","DOIUrl":"10.1038/s41536-025-00437-8","url":null,"abstract":"Notochordal cells (NC) have promise as a regenerative therapy for intervertebral disc (IVD) degeneration, but their maintenance in culture remains challenging. The study hypothesis is that nucleus pulposus (NP) cells can undergo reversion to NC-type cells through CRISPR/dCas9 activation of FoxA2. Serial passaging of cells isolated from NP shows loss of FoxA2, Brachyury (T), and Noto expression. Transient FoxA2 overexpression increased the levels of NC biomarkers, keratin, CD24, and SHH in passaged cells. So FoxA2-expressing cells were generated using CRISPR/dCas9-SAM. Analysis showed the presence of some vacuolated cells, elevated NC marker expression of Fox A2, Noto, Brachyury, and keratin and improved in vitro NP tissue formation (determined by quantifying proteoglycan content). TGFβ3 treatment enhanced tissue formation. Injected FoxA2-expressing cells survived and produced NP matrix molecules in an ex vivo bovine IVD injury model. The findings suggest FoxA2-expressing NC-type cells can be generated which may have potential to advance cell-based therapies for disc degeneration.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"49"},"PeriodicalIF":6.5,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12578846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423496","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}

引用次数: 0

Platelet derived growth factor-AB modulates post-infarct myocardium leading to extended improvement in cardiac function. 血小板衍生生长因子- ab调节梗死后心肌导致心功能的延长改善。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2025-10-22 DOI: 10.1038/s41536-025-00433-y

Tejas Deshmukh, Robert D Hume, Siqi Chen, Sindhu Igoor, Sheryl L Foster, Tony Barry, Juntang Lu, Vu Tran, Jim Pouliopoulos, Andrew Jabbour, Niv Vigder, Stuart J Cordwell, Sergey Tumanov, Christopher Nguyen, Yasuhito Kotake, Samual Turnbull, Tim Campbell, Faraz Pathan, Saurabh Kumar, Eddy Kizana, James J H Chong

{"title":"Platelet derived growth factor-AB modulates post-infarct myocardium leading to extended improvement in cardiac function.","authors":"Tejas Deshmukh, Robert D Hume, Siqi Chen, Sindhu Igoor, Sheryl L Foster, Tony Barry, Juntang Lu, Vu Tran, Jim Pouliopoulos, Andrew Jabbour, Niv Vigder, Stuart J Cordwell, Sergey Tumanov, Christopher Nguyen, Yasuhito Kotake, Samual Turnbull, Tim Campbell, Faraz Pathan, Saurabh Kumar, Eddy Kizana, James J H Chong","doi":"10.1038/s41536-025-00433-y","DOIUrl":"10.1038/s41536-025-00433-y","url":null,"abstract":"Myocardial infarction (MI) contributes to significant morbidity and mortality globally. Platelet derived growth factor-AB (PDGF-AB) is potentially a novel translational therapeutic for improving cardiac function post-MI, which we assess here using a 60 day porcine left anterior descending artery occlusion ischemia-reperfusion model. MI was induced in 10 female Landrace swine, with 5 controls, 5 receiving PDGF-AB treatment and 2 additional shams. PDGF-AB improved left ventricular ejection fraction 58 days after MI, without affecting overall infarct scar size, as shown using serial cardiac magnetic resonance imaging. Preserved infarct zone microvascular function and increased vessel maturity was also observed. Multi-omic analyses showed that PDGF-AB treatment altered the expression of proteins, metabolites, and lipids that are known to be involved in myocardial energetics and redox balance. Novel therapeutics such as PDGF-AB may lead to more sustained salvage of cardiac function by modulating the post-MI microvasculature, myocardium and extracellular matrix.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"46"},"PeriodicalIF":6.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12546596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145350041","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}

引用次数: 0

Scaffolds with spatiotemporally controlled growth factor delivery and cyclodextrin-enabled antagonism of growth factor receptor sequestration promote cutaneous wound healing. 具有时空控制生长因子递送和环糊精激活的生长因子受体隔离拮抗作用的支架可促进皮肤伤口愈合。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2025-09-29 DOI: 10.1038/s41536-025-00431-0

Jelena Marjanovic, Veronika Jurczuk, Lilian Valadares Tose, Yarixa Cintron Diaz, Francisco Fernandez Lima, Beatriz Abdo Abujamra, Sara Danker, Sinan Jabori, Devinder Singh, Jamie L Burgess, Joshua Tam, Mohamadmahdi Samandari, Rivka C Stone, Stephen C Davis, Robert S Kirsner, Marjana Tomic-Canic, Fotios M Andreopoulos, Ivan Jozic

{"title":"Scaffolds with spatiotemporally controlled growth factor delivery and cyclodextrin-enabled antagonism of growth factor receptor sequestration promote cutaneous wound healing.","authors":"Jelena Marjanovic, Veronika Jurczuk, Lilian Valadares Tose, Yarixa Cintron Diaz, Francisco Fernandez Lima, Beatriz Abdo Abujamra, Sara Danker, Sinan Jabori, Devinder Singh, Jamie L Burgess, Joshua Tam, Mohamadmahdi Samandari, Rivka C Stone, Stephen C Davis, Robert S Kirsner, Marjana Tomic-Canic, Fotios M Andreopoulos, Ivan Jozic","doi":"10.1038/s41536-025-00431-0","DOIUrl":"10.1038/s41536-025-00431-0","url":null,"abstract":"Chronic wounds present a major burden to patients, health care professionals, and health care systems worldwide, yet treatment options remain limited and often ineffective. Although initially promising, growth factor-based therapies displayed limited and underwhelming effectiveness largely due to poor bioavailabilbioity and impaired receptor function within the chronic wound microenvironment. Here we demonstrate that chronic wounds exhibit elevated cholesterol synthesis, which disrupts growth factor signaling by sequestering receptors within lipid rafts. To address this, we developed a novel therapy combining growth factors with cyclodextrin in an ECM-mimetic scaffold, enabling localized cholesterol modulation and improved receptor accessibility. We demonstrate that this approach enhances growth factor bioavailability and functionality, creating a regenerative environment. In both human ex vivo and diabetic mouse wound models, this targeted co-delivery strategy significantly improved healing outcomes by stimulating angiogenesis and re-epithelialization, supporting a promising new direction for chronic wound therapy through localized metabolic modulation of the wound niche.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"42"},"PeriodicalIF":6.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193565","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}

引用次数: 0

Exosome injection as a prevention strategy for early postoperative mesh complications in a porcine model of sacrocolpopexy. 外泌体注射作为预防猪骶髋固定模型术后早期补片并发症的策略。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2025-09-29 DOI: 10.1038/s41536-025-00432-z

Cassandra K Kisby, Sam Faraguna, Abigail Hitt, Ilya Y Shadrin, Hunter Newman, Anna Gilpin, Cindy L Amundsen, Shyni Varghese

{"title":"Exosome injection as a prevention strategy for early postoperative mesh complications in a porcine model of sacrocolpopexy.","authors":"Cassandra K Kisby, Sam Faraguna, Abigail Hitt, Ilya Y Shadrin, Hunter Newman, Anna Gilpin, Cindy L Amundsen, Shyni Varghese","doi":"10.1038/s41536-025-00432-z","DOIUrl":"10.1038/s41536-025-00432-z","url":null,"abstract":"Exosomes, an acellular regenerative biologic, have demonstrated success in resolving vaginal mesh exposures after pelvic reconstructive surgery; little data exists for their use for prevention of mesh-based complications. This study evaluated the early efficacy of purified exosome product (PEP) for preventing mesh exposures. Ten Yorkshire-crossed pigs underwent mesh sacrocolpopexy with two high-risk-for-exposure configurations: mesh fold ventrally, vaginotomy dorsally. PEP in hyaluronic acid (HA) or HA-only (control) was injected at baseline. Twelve weeks later, animals were euthanized and evaluated for mesh exposure and histologic changes. None of the PEP-treated tissues demonstrated mesh exposure (0/6); all control group animals experienced a mesh exposure (4/4 mesh fold configuration, 2/4 vaginotomy configuration). Control tissues exhibited higher fibrosis (vaginotomy fibrosis score: median(IQR); 3(3,3) control, 2(1,2) PEP; p = 0.03) and greater epithelial apoptosis (mesh fold TUNEL+area fraction: median 18.9 control vs 0.43 PEP; p = 0.02). Our study demonstrated that PEP treatment mitigated the risk of early mesh exposure.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"43"},"PeriodicalIF":6.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193577","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}

引用次数: 0

Type V collagen from macrophages regulates initial collagen assembly and alignment in post-infarcted hearts. 来自巨噬细胞的V型胶原调节梗死后心脏的初始胶原组装和排列。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2025-09-29 DOI: 10.1038/s41536-025-00430-1

Xin Sun, Sarah Sigal, Maria-Alexa Cosma, Carla de Villiers, Michael Weinberger, Paul R Riley

{"title":"Type V collagen from macrophages regulates initial collagen assembly and alignment in post-infarcted hearts.","authors":"Xin Sun, Sarah Sigal, Maria-Alexa Cosma, Carla de Villiers, Michael Weinberger, Paul R Riley","doi":"10.1038/s41536-025-00430-1","DOIUrl":"10.1038/s41536-025-00430-1","url":null,"abstract":"Previous work has revealed that macrophages directly contribute collagen to the fibrotic scar in the injured hearts of zebrafish and mice. However, the functional impact of this contribution has not been investigated. Here, we characterised the deposition and ultrastructure of collagen fibrils in the forming scar of neonatal regenerative post-natal day (P)1 hearts and fibrotic P7 and adult mouse hearts after myocardial infarction (MI). Collagen type V (Col V) was the earliest deposited fibrillar collagen, coincident with macrophage recruitment to the site of injury and prior to cardiac myo-fibroblast activation. Deletion of COL5A1 in CD68+ macrophages resulted in disarrayed collagen fibrils within the nascent scar that was associated with a trend toward chamber dilation, wall thinning and compromised cardiac function. Our findings shed light on a role for macrophage-deposited Col V in establishing collagen deposition, alignment and scar stability prior to myofibroblast activation in the immediate acute phase post-MI.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"44"},"PeriodicalIF":6.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193504","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}

引用次数: 0

Deconstruction of cellular dynamics after treatment of volumetric muscle loss injury with extracellular matrix. 细胞外基质治疗体积性肌肉损失损伤后细胞动力学的解构。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2025-09-29 DOI: 10.1038/s41536-025-00429-8

Adrienne A Giannone, Shanae A-M Butler, Jacqueline A Larouche, Paula M Fraczek, Grace Kenney, Scott A Johnson, Clint D Skillen, Pranav Rao, Jessie Jin, Teja Chaparala, Mangesh Kulkarni, Robert J Tower, Benjamin Levi, Stephen F Badylak, Bryan N Brown, Carlos A Aguilar

{"title":"Deconstruction of cellular dynamics after treatment of volumetric muscle loss injury with extracellular matrix.","authors":"Adrienne A Giannone, Shanae A-M Butler, Jacqueline A Larouche, Paula M Fraczek, Grace Kenney, Scott A Johnson, Clint D Skillen, Pranav Rao, Jessie Jin, Teja Chaparala, Mangesh Kulkarni, Robert J Tower, Benjamin Levi, Stephen F Badylak, Bryan N Brown, Carlos A Aguilar","doi":"10.1038/s41536-025-00429-8","DOIUrl":"10.1038/s41536-025-00429-8","url":null,"abstract":"The acute loss of critical skeletal muscle volume or volumetric muscle loss (VML) results in persistent inflammation, fibrotic scarring, permanent strength deficits and long-term disability. The molecular mechanisms that drive fibrosis following VML injury have primarily been evaluated in rodent models, however, translation of these findings to large animals remains underexplored. Herein, we utilized a canine model of VML and a mesoscopic approach to evaluate how treatment with an extracellular matrix hydrogel impacts the early cellular circuitry regulating inflammation, fibrosis and muscle regeneration. We observed treatment with extracellular matrix dampens inflammation and fibrosis by spatially confining the immune reaction to the superficial surface of the wound. Simultaneously, extracellular matrix treatment improved muscle stem cell and regenerative progenitor infiltration into the VML defect and limited degeneration of intact myofibers. These results establish a spatially informed framework for understanding how extracellular matrix hydrogel treatment impacts regenerative trajectories and cellular communities post-VML.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"45"},"PeriodicalIF":6.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193519","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}

引用次数: 0

FGF9 treatment reduces off-target chondrocytes from iPSC-derived kidney organoids. FGF9治疗可减少ipsc衍生肾类器官的脱靶软骨细胞。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2025-08-30 DOI: 10.1038/s41536-025-00428-9

Virginie Joris, Anika Schumacher, Maria Paula Marks, Maria Eischen-Loges, Sofia Fallo, Martijn van Griensven, Vanessa L S LaPointe

{"title":"FGF9 treatment reduces off-target chondrocytes from iPSC-derived kidney organoids.","authors":"Virginie Joris, Anika Schumacher, Maria Paula Marks, Maria Eischen-Loges, Sofia Fallo, Martijn van Griensven, Vanessa L S LaPointe","doi":"10.1038/s41536-025-00428-9","DOIUrl":"10.1038/s41536-025-00428-9","url":null,"abstract":"Renal failure due to drug nephrotoxicity or disease is frequently observed in patients. The development of in vitro models able to recapitulate kidney biology offers new possibilities to study drug toxicity or model diseases. Induced pluripotent stem cell-derived kidney organoids already show promise, but several drawbacks must be overcome to maintain them in culture, among which is the presence of non-renal cell populations such as cartilage. We modified the culture protocol and maintained kidney organoids in medium containing FGF9 for 1 additional week compared to the control protocol (Takasato). In comparison to the control, the FGF9-treated kidney organoids had reduced cartilage at day 7 + 25 and diminished chondrocyte marker expression. Importantly, the renal structures assessed by immunofluorescence were unaffected by the FGF9 treatment. This reduction of cartilage produces a higher quality kidney organoid that can be maintained longer in culture to improve their maturation for further in vivo work.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"41"},"PeriodicalIF":6.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144978465","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}

引用次数: 0