npj Regenerative Medicine最新文献_第2页

isl1a coordinates onset and termination of regeneration of the zebrafish lateral line. Isl1a协调斑马鱼侧线再生的开始和终止。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-07-01 DOI: 10.1038/s41536-026-00489-4

Paloma Meneses-Giles, Kaelan J Brennan, Nhung T T Tran, Aurélie Hintermann, Mark E Lush, Tatjana Piotrowski

{"title":"isl1a coordinates onset and termination of regeneration of the zebrafish lateral line.","authors":"Paloma Meneses-Giles, Kaelan J Brennan, Nhung T T Tran, Aurélie Hintermann, Mark E Lush, Tatjana Piotrowski","doi":"10.1038/s41536-026-00489-4","DOIUrl":"https://doi.org/10.1038/s41536-026-00489-4","url":null,"abstract":"Regenerative capacity varies widely across tissues and species. Most regeneration studies have focused on identifying genes and pathways that promote regeneration, whereas mechanisms that inhibit regeneration to enforce organ size control and prevent excessive proliferation remain less well defined. Here, we identify isl1a as a dynamically expressed negative regulator of lateral line hair cell regeneration. isl1a is highly expressed during homeostasis but becomes transiently downregulated following hair cell loss. Loss of isl1a leads to proliferative expansion of support cells, producing enlarged sensory organs with increased hair cell numbers after injury. Mechanistically, isl1a downregulation increases chromatin accessibility at pro-proliferative loci, including AP-1 transcription factors, accompanied by sustained expression of injury- and regeneration-responsive genes. Together, these findings demonstrate that injury-induced downregulation of isl1a promotes the initiation of regeneration, while its subsequent re-expression restricts the duration of the response, thereby fine-tuning hair cell regeneration and maintaining appropriate support cell numbers.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of cardiac regeneration capacity between zebrafish and medaka reveals a regenerative response in both teleost species. 比较斑马鱼和medaka之间的心脏再生能力揭示了这两种硬骨鱼物种的再生反应。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-07-01 DOI: 10.1038/s41536-026-00482-x

Miguel Angel Garitagoitia-Romero, María Galardi-Castilla, Miguel Torres, Nadia Mercader

{"title":"Comparison of cardiac regeneration capacity between zebrafish and medaka reveals a regenerative response in both teleost species.","authors":"Miguel Angel Garitagoitia-Romero, María Galardi-Castilla, Miguel Torres, Nadia Mercader","doi":"10.1038/s41536-026-00482-x","DOIUrl":"https://doi.org/10.1038/s41536-026-00482-x","url":null,"abstract":"Danio rerio (zebrafish) can regenerate their heart upon loss of over 20% of the total myocardium. A second teleost species, Oryzias latipes (medaka), however, has been described to lack this capacity and respond to a lesion forming a permanent fibrotic scar after heart resection. An altered immune response has been suggested to underlie the differences in heart regeneration. However, a thorough comparative analysis between zebrafish and medaka through the different steps of regeneration was lacking. Here, we provide an in-depth characterization of the injury response and heart regeneration in both teleost species (AB and Cab strains, respectively) after ventricular cryoinjury (CI). We observed an exacerbated neutrophil activation with little evidence of macrophage recruitment in medaka compared to zebrafish. However, cardiomyocyte proliferation significantly increased in both teleosts upon CI. We also observed transient blood vessel formation in medaka and a significant reduction of fibrotic tissue at 30 and 60 dpi compared to 7 dpi. However, some animals presented signs of an irreversible scar at 60 dpi and ventricular indentations suggestive of impaired regeneration. Nonetheless, echocardiographic assessment revealed cardiac function recovery in a subset of medaka, independent of the fibrotic tissue resolution. Overall, we conclude that the cardiac regenerative ability is broader in medaka than anticipated.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chitosan-fibrinogen-thrombin matrix accelerates re-epithelialization and cornification in a rat wound healing model. 壳聚糖-纤维蛋白原-凝血酶基质在大鼠伤口愈合模型中加速再上皮化和角化。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-06-25 DOI: 10.1038/s41536-026-00486-7

Hind Lerhcha, Anik Chevrier, Marc Lavertu

{"title":"Chitosan-fibrinogen-thrombin matrix accelerates re-epithelialization and cornification in a rat wound healing model.","authors":"Hind Lerhcha, Anik Chevrier, Marc Lavertu","doi":"10.1038/s41536-026-00486-7","DOIUrl":"10.1038/s41536-026-00486-7","url":null,"abstract":"This study evaluated a chitosan-fibrinogen-thrombin (CFT) matrix enriched with autologous skin cells and a fatty acid sodium salt (FASS) to enhance wound closure and regeneration. A rat excisional wound model compared six treatments: CFT with or without autologous cells and/or FASS, lubricating jelly, and cell suspension alone. Wounds were splinted and assessed at day 14. Tissue thickness and force at 10% strain were measured by indentation, followed by histological staining (Hematoxylin and Eosin, Masson's Trichrome, Picrosirius Red) and immunostaining (CD31, CD68, Neutrophil elastase, Arginase-1). CFT-treated wounds formed a compact crust that supported keratinocyte migration, unlike Jelly and Cells groups which had delayed closure. All wounds remained in active repair, with CFT groups showing more advanced epithelialization and cornification, but no significant benefit from adding cells or FASS. There was greater angiogenesis and presence of macrophages in all wounds versus native skin, especially in Jelly and Cells groups, indicating earlier repair phases. Picrosirius red revealed immature collagen in all treated wounds. Mechanical testing showed wound thickness and resistance similar to native skin, suggesting near-functional recovery despite incomplete maturation. The main effect came from the intrinsic properties of the CFT matrix, which provided a biocompatible barrier promoting granulation and keratinocyte migration.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334238","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

Circadian clocka regulates the zebrafish central neuronal Mauthner-cell axon regeneration via phosphodiesterase family pde4a. 生物钟通过磷酸二酯酶家族pde4a调控斑马鱼中枢神经元毛特纳细胞轴突再生。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-06-23 DOI: 10.1038/s41536-026-00488-5

Ziang Zhao, Along Han, Dinggang Fan, Keqiang Li, Junhui Zhou, Zheng Song, Bing Hu

{"title":"Circadian clocka regulates the zebrafish central neuronal Mauthner-cell axon regeneration via phosphodiesterase family pde4a.","authors":"Ziang Zhao, Along Han, Dinggang Fan, Keqiang Li, Junhui Zhou, Zheng Song, Bing Hu","doi":"10.1038/s41536-026-00488-5","DOIUrl":"10.1038/s41536-026-00488-5","url":null,"abstract":"Axon regeneration is the key to repairing spinal cord injury. Circadian rhythm plays regulatory roles in axonal regeneration. The endogenous molecular clock serves as the molecular basis for the generation and precise maintenance of circadian rhythms. CLOCK is one of the most core transcription factors in the endogenous molecular clock. However, the role of CLOCK in axon regeneration has so far remained elusive. Therefore, this study explored how the circadian gene clocka regulates the zebrafish central neuronal Mauthner cells (M-cells) axon regeneration. Using the M-cell axonal regeneration model, we found that M-cell axons exhibited circadian-phase-dependent regeneration after two-photon laser ablation, while in the clocka mutant, the circadian-phase-dependent regeneration of M-cells was deprived and their regenerative ability was inhibited. Subsequently, a combination of single-cell electroporation, single-cell capture, transcriptome sequencing, and Rolipram treatment demonstrated that clocka is required for M-cell axonal regeneration and regulates axonal regeneration through phosphodiesterase pde4a-cAMP axis. Together, these findings demonstrate that endogenous molecular clock gene clocka regulates zebrafish central M-cell axonal regeneration via pde4a-cAMP pathway and provide new insights into rhythmic regulation for central nerve repair.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148310463","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

Food-derived peptide RDP3 mitigates pyroptosis to enhance oral mucosal repair via the IL-2Rβ/PI3K axis. 食物来源的肽RDP3通过IL-2Rβ/PI3K轴减轻焦亡，增强口腔黏膜修复。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-06-20 DOI: 10.1038/s41536-026-00487-6

Junyuan Wang, Yuliu Yang, Zeqiong Ru, Yingyu Zhang, Xueying Xiong, Yujing Ding, Xin Yu, Mengfan Ma, Wenrou Su, Yihang Huang, Xinwang Yang, Naixin Liu, Ying Wang

{"title":"Food-derived peptide RDP3 mitigates pyroptosis to enhance oral mucosal repair via the IL-2Rβ/PI3K axis.","authors":"Junyuan Wang, Yuliu Yang, Zeqiong Ru, Yingyu Zhang, Xueying Xiong, Yujing Ding, Xin Yu, Mengfan Ma, Wenrou Su, Yihang Huang, Xinwang Yang, Naixin Liu, Ying Wang","doi":"10.1038/s41536-026-00487-6","DOIUrl":"10.1038/s41536-026-00487-6","url":null,"abstract":"Oral ulcers represent a prevalent mucosal disease with incompletely elucidated pathogenesis and a clinical deficiency in multifunctional therapeutics. This study investigates a food-derived peptide, RDP3, with tissue-penetrating capability, which significantly promotes repair of oral ulcer mucosal in vivo and in vitro in a low concentration (1 nM). This is the first time to report a food-origin peptide capable of accelerating oral ulcer mucosal repair. RDP3 can not only accelerate wound healing but also restore microbiome homeostasis. Mechanistically, RDP3 functions as a novel peptide-antagonist of the interleukin-2 receptor β subunit (IL-2Rβ; binding affinity KD = 0.99 μM). This interaction suppresses pathological PI3K signaling, thereby inhibiting NLRP3/GSDMD-mediated pyroptosis, reducing inflammation, and promoting mucosal regeneration. These findings position RDP3 as a promising multifunctional therapeutic candidate for oral ulcer treatment.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148297437","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

Stem cell-derived extracellular vesicles and artificial nanovesicles: a translational framework for cell-free wound repair. 干细胞来源的细胞外囊泡和人工纳米囊泡：无细胞伤口修复的翻译框架。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-06-11 DOI: 10.1038/s41536-026-00484-9

Ramya Lakshmi Rajendran, Akanksha Onkar, Rijula Batabyal, Saurabh Kumar Jha, Atharva A Mahajan, Madhurima Koley, Shouryarudra Banerjee, Arjun P, Mridul Saha, Subhrojyoti Ghosh, Anuvab Dey, Kandasamy Nagarajan ArulJothi, Eun Jung Oh, Kang Young Choi, Prakash Gangadaran, Ho Yun Chung, Byeong-Cheol Ahn

{"title":"Stem cell-derived extracellular vesicles and artificial nanovesicles: a translational framework for cell-free wound repair.","authors":"Ramya Lakshmi Rajendran, Akanksha Onkar, Rijula Batabyal, Saurabh Kumar Jha, Atharva A Mahajan, Madhurima Koley, Shouryarudra Banerjee, Arjun P, Mridul Saha, Subhrojyoti Ghosh, Anuvab Dey, Kandasamy Nagarajan ArulJothi, Eun Jung Oh, Kang Young Choi, Prakash Gangadaran, Ho Yun Chung, Byeong-Cheol Ahn","doi":"10.1038/s41536-026-00484-9","DOIUrl":"10.1038/s41536-026-00484-9","url":null,"abstract":"Chronic nonhealing wounds remain a major clinical challenge, driven by persistent inflammation, impaired angiogenesis, defective extracellular matrix remodeling, and incomplete functional restoration. While stem cell therapies can modulate these processes, their clinical use is limited by low engraftment, variability, and safety concerns. Stem cell-derived extracellular vesicles (SC-EVs) and artificial nanovesicles (SC-ANVs) have emerged as cell-free alternatives that aim to capture key paracrine functions of stem cells. In this review, we evaluate these vesicle-based approaches within a problem-oriented framework linking molecular and cellular effects to clinically meaningful outcomes. SC-EVs and SC-ANVs influence inflammation, angiogenesis, and tissue regeneration in preclinical wound models; however, current evidence is largely limited to improvements in wound closure and histological parameters. We highlight that proof of concept for clinically relevant endpoints, such as durable function, reduced scarring, and recurrence prevention, remains insufficient. Key translational challenges, including delivery, dosing, and endpoint selection, are discussed, along with a framework for future studies required to establish therapeutic efficacy. Collectively, SC-EVs and SC-ANVs represent emerging platforms whose clinical potential depends on rigorous validation against defined clinical benchmarks.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229000","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

Enhanced exosomes for fertility protection against chemotherapy-induced ovarian damage. 增强外泌体对化疗引起的卵巢损伤的生育保护作用。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-06-04 DOI: 10.1038/s41536-026-00477-8

Mohammad Mousaei Ghasroldasht, Hang-Soo Park, Farzana Liakath Ali, Jin Seok, Analea Beckman, Samar Alkhrait, Mervat M Omran, Hiba Alkelani, Nina Hafner, Hyunho Kim, Ayman Al-Hendy

{"title":"Enhanced exosomes for fertility protection against chemotherapy-induced ovarian damage.","authors":"Mohammad Mousaei Ghasroldasht, Hang-Soo Park, Farzana Liakath Ali, Jin Seok, Analea Beckman, Samar Alkhrait, Mervat M Omran, Hiba Alkelani, Nina Hafner, Hyunho Kim, Ayman Al-Hendy","doi":"10.1038/s41536-026-00477-8","DOIUrl":"10.1038/s41536-026-00477-8","url":null,"abstract":"Exosome-based therapies are emerging as promising tools in regenerative medicine and tissue protection. In this study, we engineered exosomes by mimicking paracrine signaling between umbilical cord-derived mesenchymal stem cells (UC-MSCs) and granulosa cells to mitigate chemotherapy-induced ovarian toxicity. Enhanced exosomes were evaluated in vitro, in vivo, and ex vivo using human granulosa cells, cyclophosphamide-treated mice, and cultured ovarian tissues from humans and rats. Enhanced exosomes demonstrated protective effects compared with chemotherapy-only controls. Molecular analyses revealed increased pro-proliferative and anti-apoptotic gene expression and reduced apoptotic markers following treatment. In vivo, enhanced exosome administration was associated with 70% higher primordial follicle counts and a two-fold increase in combined primordial and primary follicles relative to CTX controls. Primary follicle numbers were markedly elevated ( > 20-fold vs CTX). In breeding studies, pup numbers increased from 1 in CTX-treated mice to 7 in enhanced exosome-treated mice in the first mating, and pregnancies were observed in later breeding rounds only in the enhanced group. Enhanced exosomes also modulated ATP-binding cassette transporter expression. In human ovarian tissue ex vivo, treatment resulted in a two-fold increase in AMHR2 expression. These findings support engineered exosomes as a potential platform for oncofertility preservation and mitigation of chemotherapy-associated gonadotoxicity.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148165497","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

Impaired bone healing upon neutrophil-specific adrenoreceptor beta 2 knockout in non-osteoporotic and osteoporotic mice. 中性粒细胞特异性肾上腺素受体β 2敲除对非骨质疏松和骨质疏松小鼠骨愈合的影响。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-05-28 DOI: 10.1038/s41536-026-00481-y

Sandra Dieterich, Nico Gläser, Christoph Kölbl, Dorothea Gebauer, Jana Bleher, Oliver Küppers, Verena Fischer, Anita Ignatius, Melanie Haffner-Luntzer

{"title":"Impaired bone healing upon neutrophil-specific adrenoreceptor beta 2 knockout in non-osteoporotic and osteoporotic mice.","authors":"Sandra Dieterich, Nico Gläser, Christoph Kölbl, Dorothea Gebauer, Jana Bleher, Oliver Küppers, Verena Fischer, Anita Ignatius, Melanie Haffner-Luntzer","doi":"10.1038/s41536-026-00481-y","DOIUrl":"10.1038/s41536-026-00481-y","url":null,"abstract":"After a bone fracture, osteoporotic mice show delayed healing associated with elevated systemic inflammation and increased neutrophil numbers in the early fracture hematoma. Because short-term treatment with the beta-adrenoreceptor-blocker propranolol reduced neutrophil recruitment, we hypothesized that deletion of β2-adrenoreceptor (Adrb2) signaling in neutrophils would normalize neutrophil recruitment and accelerate bone healing in osteoporotic mice. A conditional Adrb2 knockout in Ly6G⁺ neutrophils was generated using Ly6G-Cre Adrb2-flox mice. Bone and immune phenotypes were analyzed via µCT and histology under non-fracture conditions and during bone healing in ovariectomized postmenopausal mice. Both non-osteoporotic and osteoporotic female Ly6G-Adrb2-KO mice showed impaired bone healing vs. controls, while only minor bone alterations were observed under non-fracture conditions. Pathway analysis of isolated neutrophils, characterized by RNA-sequencing, suggested reduced neutrophil activation and disturbed neutrophil/mast cell interactions upon Ly6G-Adrb2-KO. Summarily, our data demonstrate that Adrb2 signaling is important for neutrophil recruitment and seems to be critical for proper bone healing.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"11 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13219604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148058345","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

Author Correction: Parishin A-loaded mesoporous silica nanoparticles modulate macrophage polarization to attenuate tendinopathy. 作者更正：Parishin a负载的介孔二氧化硅纳米颗粒调节巨噬细胞极化以减轻肌腱病变。

IF 6.5 1区医学

npj Regenerative Medicine Pub Date : 2026-05-28 DOI: 10.1038/s41536-026-00480-z

Lisha Zhu, Yu Wang, Shanshan Jin, Yuting Niu, Min Yu, Zixin Li, Liyuan Chen, Xiaolan Wu, Chengye Ding, Tianhao Wu, Xinmeng Shi, Yixin Zhang, Dan Luo, Yan Liu

引用次数: 0

Engineering the oxygen microenvironment for pancreatic islet transplants. 胰岛移植的氧微环境工程。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-05-20 DOI: 10.1038/s41536-026-00479-6

Samantha Kruzshak, Flannery G Williams, Gulden Camci-Unal, Emmanuel S Tzanakakis

引用次数: 0