npj Regenerative Medicine最新文献_第5页

Adipose-derived dual cell therapy enhances arteriogenesis and limb preservation through vascular integration in critical limb ischemia. 脂肪源性双细胞治疗通过血管整合在严重肢体缺血中增强动脉生成和肢体保存。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-01-27 DOI: 10.1038/s41536-026-00458-x

Do Young Kim, Dae Yeon Hwang, Gabee Park, Yeon Ju Song, Jiwon Kang, Youngsook Son, Sung Vin Yim, Hyun Sook Hong

{"title":"Adipose-derived dual cell therapy enhances arteriogenesis and limb preservation through vascular integration in critical limb ischemia.","authors":"Do Young Kim, Dae Yeon Hwang, Gabee Park, Yeon Ju Song, Jiwon Kang, Youngsook Son, Sung Vin Yim, Hyun Sook Hong","doi":"10.1038/s41536-026-00458-x","DOIUrl":"10.1038/s41536-026-00458-x","url":null,"abstract":"Peripheral artery disease (PAD) causes progressive arterial narrowing in the lower limbs and can advance to critical limb ischemia (CLI). Limited revascularization options highlight the need for safer, more effective therapies. Vascular multipotent stem cells (VMSCs) and adipose-derived stem cells (ADSCs) were isolated from adipose tissue, characterized phenotypically, and tested for angiogenic activity in vitro. Their therapeutic efficacy was then examined in a murine critical limb ischemia model through intramuscular transplantation, assessing limb preservation, neovascularization, and cell integration. VMSCs shared mesenchymal stem cell-like features with ADSCs and exhibited robust proliferative capacity, enabling rapid expansion to clinically relevant numbers. VMSCs also demonstrated endothelial-like properties, including CD31, VE-cadherin, and CD141 expression, and formed capillary-like structures in vitro. In contrast, ADSCs displayed perivascular characteristics with α-SMA and Transgelin expression. Co-culture of VMSCs and ADSCs promoted the development of mature tubular networks in vitro. Combined cell transplantation markedly decreased limb loss and promoted both angiogenesis and arteriogenesis in ischemic tissue, with transplanted cells partially integrating into the host vasculature to form hybrid vascular structures. VMSCs and ADSCs show complementary regenerative functions, sustained engraftment, and support for large-vessel formation, underscoring their potential for stem cell-based vascular therapies.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146068593","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

Engraftment of wild-type alveolar type II epithelial cells in surfactant protein C deficient mice. 表面活性剂蛋白C缺乏小鼠野生型肺泡II型上皮细胞的移植。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2026-01-20 DOI: 10.1038/s41536-026-00455-0

Camilla Predella, Lauren Lapsley, Keyue Ni, Tania A Thimraj, Hsiao-Yun Liu, John W Murray, Joshua E Motelow, Hans-Willem Snoeck, Stephan W Glasser, Anjali Saqi, N Valerio Dorrello

{"title":"Engraftment of wild-type alveolar type II epithelial cells in surfactant protein C deficient mice.","authors":"Camilla Predella, Lauren Lapsley, Keyue Ni, Tania A Thimraj, Hsiao-Yun Liu, John W Murray, Joshua E Motelow, Hans-Willem Snoeck, Stephan W Glasser, Anjali Saqi, N Valerio Dorrello","doi":"10.1038/s41536-026-00455-0","DOIUrl":"10.1038/s41536-026-00455-0","url":null,"abstract":"Childhood interstitial lung disease (chILD) secondary to pulmonary surfactant deficiency is a devastating chronic lung disease in children. Clinical presentation includes mild to severe respiratory failure and fibrosis. There is no specific treatment, except lung transplantation, which is hampered by a severe shortage of donor organs, especially for young patients. Repair of lungs with chILD represents a longstanding therapeutic challenge but cell therapy is a promising strategy. As surfactant is produced by alveolar epithelial type II (ATII) cells, engraftment with normal or gene-corrected ATII cells might provide an avenue to cure. Here, we used a chILD disease-like model, Sftpc-/- mice, to provide proof-of-principle for this approach. Sftpc-/- mice developed chronic interstitial lung disease with age and were hypersensitive to bleomycin. We could engraft wild-type ATII cells after low dose bleomycin conditioning. Transplanted ATII cells produced mature SPC and attenuated bleomycin-induced lung injury up to two months post-transplant. This study demonstrates that partial replacement of mutant ATII cells can promote lung repair in a mouse model of chILD-like disease.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":"11"},"PeriodicalIF":6.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004639","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

Inhibition of CDK8 rescues impaired ischemic fracture healing. 抑制CDK8可挽救缺血性骨折愈合受损。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2026-01-17 DOI: 10.1038/s41536-026-00456-z

Christina A Capobianco, Michelle J Song, Easton C Farrell, Alexander J Knights, Karen Kessell, Alexis Donneys, Jeanna T Schmanski, Luke R Schroeder, Mengqian Chen, Igor B Roninson, Yadav Wagley, Tristan Maerz, Kurt D Hankenson

{"title":"Inhibition of CDK8 rescues impaired ischemic fracture healing.","authors":"Christina A Capobianco, Michelle J Song, Easton C Farrell, Alexander J Knights, Karen Kessell, Alexis Donneys, Jeanna T Schmanski, Luke R Schroeder, Mengqian Chen, Igor B Roninson, Yadav Wagley, Tristan Maerz, Kurt D Hankenson","doi":"10.1038/s41536-026-00456-z","DOIUrl":"10.1038/s41536-026-00456-z","url":null,"abstract":"Annually, 10% of 15 million bone fractures in the US fail to heal, and fractures with compromised blood flow, i.e., ischemia, are five times more likely to become nonunions. While ischemia is known to impair healing, the cellular and molecular mechanisms underlying this deficiency are unclear. Wild-type mice with surgically-induced ischemia underwent tibia fractures, and single-cell RNA-sequencing was performed on calluses at days 4 and 7 post-fracture. We observed delayed chondrogenic differentiation and upregulation of Cyclin-Dependent Kinase 8 (Cdk8) by stromal progenitors and fibroblasts in the ischemic callus. Hypoxia induced CDK8 gene expression in human mesenchymal stromal cells (hMSC), and pharmacological CDK8 inhibition promoted hMSC chondrogenic and osteogenic potential. In vivo oral delivery of a CDK8 inhibitor enhanced callus chondrogenesis and mineralization, potentially improving ischemic fracture healing. Our results suggest that CDK8 impedes stromal cell differentiation and that its inhibition may be a clinically translatable approach to enhance ischemic fracture healing.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":"12"},"PeriodicalIF":6.5,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994748","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

CD73 overexpression in ADSCs accelerates bladder repair by regulating the NFκB/NLRP3/caspase-1 signaling axis in neurogenic bladder rats. ADSCs中CD73过表达通过调节神经源性膀胱大鼠NFκB/NLRP3/caspase-1信号轴加速膀胱修复。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2026-01-17 DOI: 10.1038/s41536-026-00454-1

Guanqun Zhu, Rui Zhang, Jiao Huang, Zongliang Zhang, Kai Zhao, Xinbao Yin, Xiaokun Yang, Zaiqing Jiang, Han Yang, Woong Jin Bae, Ke Wang

{"title":"CD73 overexpression in ADSCs accelerates bladder repair by regulating the NFκB/NLRP3/caspase-1 signaling axis in neurogenic bladder rats.","authors":"Guanqun Zhu, Rui Zhang, Jiao Huang, Zongliang Zhang, Kai Zhao, Xinbao Yin, Xiaokun Yang, Zaiqing Jiang, Han Yang, Woong Jin Bae, Ke Wang","doi":"10.1038/s41536-026-00454-1","DOIUrl":"10.1038/s41536-026-00454-1","url":null,"abstract":"Neurogenic bladder (NB) is a disabling condition lacking effective therapies. This study investigated whether CD73-expressing adipose-derived stem cells (ADSCs) promote bladder repair in a rat model of NB and explored the underlying mechanisms. ADSCs were sorted into CD73⁺ and CD73⁻ populations, and CD73⁺ cells were further modified to generate CD73⁺/ev ADSCs and CD73-overexpressing CD73⁺/⁺ADSCs, while CD73 inhibition was achieved using APCP. Conditioned media were applied to rat bladder smooth muscle cells in vitro, and ADSCs were injected into the bladder wall of rats subjected to bilateral pelvic nerve crush. Four weeks after treatment, bladder function, histology, and molecular markers were evaluated. CD73 overexpression enhanced VEGF and SDF-1 expression, promoted cell proliferation, and reduced inflammatory cytokines, whereas APCP suppressed VEGF. In vivo, CD73⁺/⁺ADSCs improved cystometric parameters, regenerated bladder tissue, reduced pyroptosis, and activated the PI3K/AKT/mTOR pathway, while suppressing NF-κB/NLRP3/caspase-1 signaling. CD73 expression and VEGF progressively declined in untreated NB rats but were restored by CD73⁺/⁺ADSCs. These findings indicate that CD73 enhances ADSC-mediated bladder repair through dual pro-regenerative and anti-inflammatory actions, suggesting a promising therapeutic strategy for NB.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":"10"},"PeriodicalIF":6.5,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994755","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

Activated Hedgehog signaling in keratocytes leads to stromal stiffness and impairs corneal regeneration. 角化细胞中激活的刺猬信号导致基质僵硬并损害角膜再生。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2026-01-15 DOI: 10.1038/s41536-026-00453-2

Qian Yu, Ping Li, Zhirui Du, Manju Che, Hui Zhao, Baojie Li, Peiquan Zhao, Jing Li

{"title":"Activated Hedgehog signaling in keratocytes leads to stromal stiffness and impairs corneal regeneration.","authors":"Qian Yu, Ping Li, Zhirui Du, Manju Che, Hui Zhao, Baojie Li, Peiquan Zhao, Jing Li","doi":"10.1038/s41536-026-00453-2","DOIUrl":"10.1038/s41536-026-00453-2","url":null,"abstract":"The repair of corneal injuries remains a major challenge in clinical practice. Impaired corneal wound healing is closely associated with aberrantly activated stromal keratocytes and disorganized extracellular matrix. Here, we identify aberrant Hedgehog signaling in corneal keratocytes as a key driver of defective wound repair. In adult mice, Hedgehog signaling is suppressed in quiescent keratocytes but is pathologically reactivated following chemical injury, correlating with impaired repair. Keratocyte-specific Hedgehog activation via Ptch1 ablation disrupted corneal wound healing after epithelial scraping-a process that would normally resolve seamlessly under physiological conditions. Mechanistically, Hedgehog activation induced stromal thinning and stiffening through disorganized collagen fibrils. Transcriptomics analysis revealed keratocyte transdifferentiation into fibroblast-like phenotypes, accompanied by downregulation of extracellular matrix genes. Hedgehog-mediated stromal stiffening suppressed YAP activity in the overlying epithelium via Hippo pathway activation, blocking epithelial differentiation-a defect that was reversed by Hippo inhibition (XMU-MP-1). In chemical injury models, genetic Smo deletion or pharmacological Gli1/2 inhibition (GANT61) restored stromal architecture, normalized collagen organization, and rescued epithelial differentiation defects. These findings establish Hedgehog signaling in keratocytes as a critical regulator of stromal-epithelial crosstalk and highlight its targeted inhibition as a potential therapeutic strategy to restore corneal transparency and repair fidelity after injury.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":"9"},"PeriodicalIF":6.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991683","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

Optimized biomechanical design of a tissue engineered pulsatile Fontan conduit. 组织工程脉冲方丹导管生物力学优化设计。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2026-01-15 DOI: 10.1038/s41536-025-00450-x

Nir Emuna, Zinan Hu, Alison L Marsden, Jay D Humphrey

{"title":"Optimized biomechanical design of a tissue engineered pulsatile Fontan conduit.","authors":"Nir Emuna, Zinan Hu, Alison L Marsden, Jay D Humphrey","doi":"10.1038/s41536-025-00450-x","DOIUrl":"10.1038/s41536-025-00450-x","url":null,"abstract":"Children with congenital heart defects increasingly survive to adulthood, but the non-physiological Fontan circulation imposed by current surgical palliation leads to significant sequelae and reduced lifespan. Restoring subpulmonic pumping function remains a long-standing goal, and there have been several attempts using regenerative medicine approaches. These efforts have lacked biomechanical rigor, however, and have not achieved the requisite functionality. Here, we introduce an analytically based framework that grounds pulsatile conduit design in biomechanical principles, coupling the architecture and properties of a passive matrix with embedded myofibers to optimize performance within pediatric anatomical constraints. Parametric exploration of matrix properties and myofiber orientations yields biomechanically feasible designs. Sensitivity analyses demonstrate design robustness and highlight parameters critical for reproducible biomanufacturing and surgical implementation. To illustrate clinical potential, a patient-specific lumped-parameter hemodynamic model shows that an optimized pulsatile conduit can generate physiologically meaningful pressures and flows and outperform passive grafts.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":"6"},"PeriodicalIF":6.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12859017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991694","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

Intrinsic muscle stem cell dysfunction underlies functional deficits in models of type 1 diabetes. 内在肌肉干细胞功能障碍是1型糖尿病模型功能缺陷的基础。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2026-01-06 DOI: 10.1038/s41536-025-00452-9

Jin D Chung, Jennifer Trieu, Benjamin L Parker, John H Nguyen, Annabel Chee, Audrey S Chan, Abhirup Jayasimhan, Devy Deliyanti, Peter J Houweling, Holly K Voges, Karly C Sourris, Richard J Mills, Melinda T Coughlan, Jennifer L Wilkinson-Berka, Enzo R Porrello, Gordon S Lynch

{"title":"Intrinsic muscle stem cell dysfunction underlies functional deficits in models of type 1 diabetes.","authors":"Jin D Chung, Jennifer Trieu, Benjamin L Parker, John H Nguyen, Annabel Chee, Audrey S Chan, Abhirup Jayasimhan, Devy Deliyanti, Peter J Houweling, Holly K Voges, Karly C Sourris, Richard J Mills, Melinda T Coughlan, Jennifer L Wilkinson-Berka, Enzo R Porrello, Gordon S Lynch","doi":"10.1038/s41536-025-00452-9","DOIUrl":"10.1038/s41536-025-00452-9","url":null,"abstract":"Muscle function and regeneration are impaired in type 1 diabetes, but whether this arises directly from muscle stem cell (MuSC) dysfunction has not been addressed. Here, we utilized three-dimensional MuSC cultures (micromuscles) to demonstrate that hyperglycemia drives deficits in muscle stem cell function, leading to impaired force production in differentiated myotubes. The functional capacity of skeletal muscle was shown to decline after repeated bouts of injury in mouse models of type 1 diabetes, and this was replicated in micromuscles derived from MuSCs isolated from diabetic mice, indicating MuSC dysfunction was linked to poor muscle regeneration and function. The loss of force producing capacity was associated with impaired myotube hypertrophy in vitro and in vivo after injury. Furthermore, poor muscle regeneration was exacerbated by a loss of MuSC number due to aberrant activation, even in the absence of injury. Deficits in MuSC function and number could be rescued by early treatment with the glucose-lowering drug dapagliflozin, indicating that MuSC defects were driven by exposure to a hyperglycemic environment. The findings reveal that MuSC dysfunction contributes to muscle functional deficits in models of type 1 diabetes.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":"8"},"PeriodicalIF":6.5,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12873224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913962","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

Spatiotemporal dynamics and regulation of suture morphology and collagen remodeling during trans-sutural distraction osteogenesis. 缝线牵张成骨过程中缝线形态和胶原重塑的时空动态和调控。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2026-01-05 DOI: 10.1038/s41536-025-00448-5

Zhiyu Lin, Yujie Chen, Peiyang Zhang, Mengying Jin, Yan Zha, Zhenmin Zhao

{"title":"Spatiotemporal dynamics and regulation of suture morphology and collagen remodeling during trans-sutural distraction osteogenesis.","authors":"Zhiyu Lin, Yujie Chen, Peiyang Zhang, Mengying Jin, Yan Zha, Zhenmin Zhao","doi":"10.1038/s41536-025-00448-5","DOIUrl":"10.1038/s41536-025-00448-5","url":null,"abstract":"Trans-sutural distraction osteogenesis (TSDO) is an effective treatment of midfacial hypoplasia, a craniofacial deformity frequently associated with cleft lip and palate. Though extracellular matrix (ECM) remodeling plays a pivotal role in craniofacial correction, the characteristics and mechanisms underlying collagen reorganization and cellular morphological adaptations during TSDO remain poorly understood. This study quantitatively delineates the spatiotemporal changes of sutural cells and ECM morphology, revealing a polarized alignment parallel to the direction of mechanical force. Multi-omics analysis demonstrates that macrophages regulate collagen remodeling in suture mesenchymal stem cells (SuSCs) via the PDGF signaling pathway. Subsequent in vitro stretch loading models confirmed PDGF pathway activation enhances SuSCs migration, collagen synthesis, and cellular morphological reorganization. Validation in macrophage-elimination murine models further corroborated this regulatory axis. Collectively, our work maps the dynamic microenvironmental changes during TSDO and elucidates cell-cell interaction-driven ECM collagen remodeling. These insights advance the understanding of TSDO-mediated osteogenesis and provide a foundation for developing optimized therapeutic strategies.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":"4"},"PeriodicalIF":6.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12847925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907400","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

Disease exacerbation in human DMD MYOrganoids enables gene therapy evaluation and unveils persistence of fibrotic activity. 人类DMD myorganoid的疾病恶化使基因治疗评估和揭示纤维化活动的持久性成为可能。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-01-02 DOI: 10.1038/s41536-025-00445-8

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":"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/s41536-025-00445-8","DOIUrl":"10.1038/s41536-025-00445-8","url":null,"abstract":"Leading gene therapy approaches for Duchenne muscular dystrophy (DMD) using AAV-mediated delivery of microdystrophin (µDys) have shown partial efficacy in patients, contrasting with the favorable outcomes observed in animal models. The identification of effective therapeutic strategies could be accelerated by using human high-throughput DMD models that replicate the molecular complexity driving pathology for accurate screening. To face this challenge, we develop MYOrganoids, an engineered muscle platform derived from patient-induced pluripotent stem cells (iPSC), recapitulating critical hallmarks of DMD, such as fibrosis and muscle dysfunction. We show that co-culture of fibroblasts with iPSC-derived muscle cells during organoid generation is pivotal for functional maturation and muscle force evaluation upon eccentric contractions. Notably, incorporation of DMD fibroblasts induced phenotypic exacerbation in DMD MYOrganoids by unraveling of fibrotic signature and fatiguability through cell-contact and paracrine mechanisms. We then exploited our system to interrogate gene therapy efficacy in this severe context. Although µDys gene transfer improves muscle resistance and partially restores membrane stability, it fails to reduce profibrotic signaling. These findings highlight the persistence of fibrotic activity post-gene therapy in our system, a limitedly explored aspect in DMD models, and provide the opportunity to study mechanisms of dysregulated cellular communication and empower gene therapy efficacy.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":"2"},"PeriodicalIF":7.0,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897102","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

Paracrine effect of human stem cell-derived progenitor cells on remodeling of the vagina. 人干细胞衍生祖细胞对阴道重塑的旁分泌作用。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2025-12-31 DOI: 10.1038/s41536-025-00449-4

Bo Yu, Yan Wen, Kayla Jiwon Kim, Amy Diane Dobberfuhl, Bertha Chen

{"title":"Paracrine effect of human stem cell-derived progenitor cells on remodeling of the vagina.","authors":"Bo Yu, Yan Wen, Kayla Jiwon Kim, Amy Diane Dobberfuhl, Bertha Chen","doi":"10.1038/s41536-025-00449-4","DOIUrl":"10.1038/s41536-025-00449-4","url":null,"abstract":"Pelvic organ prolapse (POP) due to weak support tissues is a common, debilitating condition typically treated with surgery. However, surgery is suboptimal due to associated risks and high prolapse recurrence rates. Therefore, there is a need for non-surgical therapies to restore supportive tissues, such as the vagina, following surgical intervention. In this study, we used patient induced pluripotent stem cells as a source to generate patient-specific progenitors of smooth muscle cells (pSMCs) and collected secretomes from these progenitor cells to examine their paracrine effects. Proteomic analysis of the conditioned media from pSMCs (pSMC-CM), which contain the secretomes, revealed proteins involved in extracellular matrix (ECM) remodeling. We assessed the paracrine effect of pSMC-CM using vaginal fibroblasts from POP patients and in a rat model of surgically injured vagina. pSMC-CM increased ECM protein expression in human vaginal fibroblasts and enhanced vaginal contractile function and ECM protein deposition in the surgically injured rat vagina. These findings suggest that pSMC-CM may promote vaginal contractile function and tissue extracellular matrix remodeling following surgical intervention.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":"5"},"PeriodicalIF":6.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12847989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879440","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