npj Regenerative Medicine最新文献

Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing.

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2025-02-04 DOI: 10.1038/s41536-024-00382-y

Margeaux Hodgson-Garms, Matthew J Moore, Mikaël M Martino, Kilian Kelly, Jessica E Frith

{"title":"Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing.","authors":"Margeaux Hodgson-Garms, Matthew J Moore, Mikaël M Martino, Kilian Kelly, Jessica E Frith","doi":"10.1038/s41536-024-00382-y","DOIUrl":"https://doi.org/10.1038/s41536-024-00382-y","url":null,"abstract":"Much of the therapeutic potential of mesenchymal stromal cells (MSCs) is underpinned by their secretome which varies significantly with source, donor and microenvironmental cues. Understanding these differences is essential to define the mechanisms of MSC-based tissue repair and optimise cell therapies. This study analysed the secretomes of bone-marrow (BM.MSCs), umbilical-cord (UC.MSCs), adipose-tissue (AT.MSCs) and clinical/commercial-grade induced pluripotent stem cell-derived MSCs (iMSCs), under resting and inflammatory licenced conditions. iMSCs recapitulated the inflammatory licensing process, validating their comparability to tissue-derived MSCs. Overall, resting secretomes were defined by extracellular matrix (ECM) and pro-regenerative proteins, while licensed secretomes were enriched in chemotactic and immunomodulatory proteins. iMSC and UC.MSC secretomes contained proteins indicating proliferative potential and telomere maintenance, whereas adult tissue-derived secretomes contained fibrotic and ECM-related proteins. The data and findings from this study will inform the optimum MSC source for particular applications and underpin further development of MSC therapies.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"7"},"PeriodicalIF":6.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191182","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

Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels.

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2025-02-04 DOI: 10.1038/s41536-024-00385-9

Fang Chen, Uiyoung Han, Thitima Wungcharoen, Youngyoon Amy Seo, Peter Le, Li Jiang, Nae-Won Kang, Euisun Song, Kyeongwoo Jang, David Mundy, Gabriella Maria Fernandes-Cunha, Sarah Heilshorn, David Myung

{"title":"Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels.","authors":"Fang Chen, Uiyoung Han, Thitima Wungcharoen, Youngyoon Amy Seo, Peter Le, Li Jiang, Nae-Won Kang, Euisun Song, Kyeongwoo Jang, David Mundy, Gabriella Maria Fernandes-Cunha, Sarah Heilshorn, David Myung","doi":"10.1038/s41536-024-00385-9","DOIUrl":"https://doi.org/10.1038/s41536-024-00385-9","url":null,"abstract":"Corneal transplantation is the primary treatment for corneal blindness, affecting millions globally. However, challenges like donor scarcity and surgical complications remain. Recently, in situ-forming corneal stroma substitutes have emerged, offering potential solutions to these limitations. These substitutes enable liquid-to-hydrogel formation in situ, eliminating sutures and reducing complications. Here we performed a direct, side-by-side comparison of a composite hyaluronan-collagen (HA-Col) hydrogel crosslinked by either photochemistry or bio-orthogonal chemistry to ascertain the impact of reaction specificity on corneal wound healing. Testing in rodent and rabbit models suggests that composite HA-Col gels crosslinked by bio-orthogonal chemistry results in more rapid and optically favorable wound healing compared to the same composition crosslinked by photochemistry as well as bio-orthogonally crosslinked collagen alone. These findings underscore biochemical parameters that may be important to the success of crosslinked, in situ-forming hydrogels as an alternative to corneal transplantation, with the potential for expanded access to treatment and improved outcomes.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"8"},"PeriodicalIF":6.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191181","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

Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse.

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2025-01-22 DOI: 10.1038/s41536-025-00393-3

Maria Elena Candela, Melisande Addison, Rhona Aird, Tak-Yung Man, Jennifer A Cartwright, Candice Ashmore-Harris, Alastair M Kilpatrick, Philip J Starkey Lewis, Anna Drape, Mark Barnett, Donna Mitchell, Colin McLean, Neil McGowan, Marc Turner, James W Dear, Stuart J Forbes

{"title":"Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse.","authors":"Maria Elena Candela, Melisande Addison, Rhona Aird, Tak-Yung Man, Jennifer A Cartwright, Candice Ashmore-Harris, Alastair M Kilpatrick, Philip J Starkey Lewis, Anna Drape, Mark Barnett, Donna Mitchell, Colin McLean, Neil McGowan, Marc Turner, James W Dear, Stuart J Forbes","doi":"10.1038/s41536-025-00393-3","DOIUrl":"10.1038/s41536-025-00393-3","url":null,"abstract":"Acute liver failure is a rapidly progressing, life-threatening condition most commonly caused by an overdose of acetaminophen (paracetamol). The antidote, N-acetylcysteine (NAC), has limited efficacy when liver injury is established. If acute liver damage is severe, liver failure can rapidly develop with associated high mortality rates. We have previously demonstrated that alternatively, activated macrophages are a potential therapeutic option to reverse acute liver injury in pre-clinical models. In this paper, we present data using cryopreserved human alternatively activated macrophages (hAAMs)-which represent a potential, rapidly available treatment suitable for use in the acute setting. In a mouse model of APAP-induced injury, peripherally injected cryopreserved hAAMs reduced liver necrosis, modulated inflammatory responses, and enhanced liver regeneration. hAAMs were effective even when administered after the therapeutic window for NAC. This cell therapy approach represents a potential treatment for APAP overdose when NAC is ineffective because liver injury is established.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"5"},"PeriodicalIF":6.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025789","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

Revitalizing the heart: strategies and tools for cardiomyocyte regeneration post-myocardial infarction.

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2025-01-22 DOI: 10.1038/s41536-025-00394-2

Axelle Bois, Catarina Grandela, James Gallant, Christine Mummery, Philippe Menasché

引用次数: 0

Systemic factors associated with antler growth promote complete wound healing. 与鹿角生长有关的全身因素促进伤口完全愈合。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2025-01-21 DOI: 10.1038/s41536-025-00391-5

Qianqian Guo, Guokun Zhang, Jing Ren, Jiping Li, Zhen Wang, Hengxing Ba, Zihao Ye, Ying Wang, Junjun Zheng, Chunyi Li

{"title":"Systemic factors associated with antler growth promote complete wound healing.","authors":"Qianqian Guo, Guokun Zhang, Jing Ren, Jiping Li, Zhen Wang, Hengxing Ba, Zihao Ye, Ying Wang, Junjun Zheng, Chunyi Li","doi":"10.1038/s41536-025-00391-5","DOIUrl":"10.1038/s41536-025-00391-5","url":null,"abstract":"Deer antlers are the only mammalian appendages that can fully regenerate from periosteum of pedicles (PP). This regeneration process starts from regenerative healing of wounds. Removal of PP abolishes antler regeneration, however, the regenerative cutaneous wound healing proceeds, indicating that some factors in the circulation contribute to this healing. In this study, we produced a wound in the scalp of deer either in antler regeneration period (ARP) (n = 3) or in non-ARP (n = 3). Results showed full regeneration took place only when the wound was created during ARP. Interestingly, topical application of systemic factors from ARP (n = 9) promoted regenerative wound healing in rats. Comparative proteomics analysis (n = 3) revealed that PRG4 and IGF-1 were high during ARP, and topical application of PRG4 + IGF-1 promoted restoration in rat FTE wounds. We believe that, ultimately, incorporating systemic factors into advanced wound care modalities could offer new opportunities for regenerative healing in the clinical setting.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"4"},"PeriodicalIF":6.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016227","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

Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing. Hedgehog信号传导指导细胞分化并在肌腱末端愈合中发挥关键作用。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2025-01-20 DOI: 10.1038/s41536-025-00392-4

Fei Fang, Matthew Casserly, Julia Robbins, Stavros Thomopoulos

{"title":"Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing.","authors":"Fei Fang, Matthew Casserly, Julia Robbins, Stavros Thomopoulos","doi":"10.1038/s41536-025-00392-4","DOIUrl":"10.1038/s41536-025-00392-4","url":null,"abstract":"A high prevalence of rotator cuff tears presents a major clinical challenge. A better understanding of the molecular mechanisms underlying enthesis development and healing is needed for developing treatments. We recently identified hedgehog (Hh)-lineage cells critical for enthesis development and repair. This study revealed cell-cell communication within the Hh-lineage cell population. To further characterize the role of Hh signaling, we used mouse models to activate and inactivate the Hh pathway in enthesis progenitors. Activation of Hh target genes during enthesis development increased its mineralization and mechanical properties. Activation of Hh signaling at the injured mature enthesis promoted fibrocartilage formation, enhanced mineralization, and increased expression of chondrogenic and osteogenic markers, which implies that Hh signaling drives cell differentiation to regenerate the damaged enthesis. Conversely, deletion of Hh target genes impaired enthesis healing. In summary, this study revealed a new strategy for enthesis repair via activation of Hh signaling in endogenous cells.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"3"},"PeriodicalIF":6.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016153","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

Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model. 在非人灵长类动物缺血/再灌注模型中，免疫抑制心肌细胞治疗中的肠道微生物群调节。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2025-01-15 DOI: 10.1038/s41536-025-00390-6

Hung-Chih Chen, Yu-Che Cheng, Marvin L Hsieh, Po-Ju Lin, Emily F Wissel, Theodore Steward, Cindy M C Chang, Jennifer Coonen, Timothy A Hacker, Timothy J Kamp, Patrick C H Hsieh

{"title":"Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model.","authors":"Hung-Chih Chen, Yu-Che Cheng, Marvin L Hsieh, Po-Ju Lin, Emily F Wissel, Theodore Steward, Cindy M C Chang, Jennifer Coonen, Timothy A Hacker, Timothy J Kamp, Patrick C H Hsieh","doi":"10.1038/s41536-025-00390-6","DOIUrl":"10.1038/s41536-025-00390-6","url":null,"abstract":"Gut microbiota affect transplantation outcomes; however, the influence of immunosuppression and cell therapy on the gut microbiota in cardiovascular care remains unexplored. We investigated gut microbiota dynamics in a nonhuman primate (NHP) cardiac ischemia/reperfusion model while under immunosuppression and receiving cell therapy with human induced pluripotent stem cell (hiPSC)-derived endothelial cells (EC) and cardiomyocytes (CM). Both immunosuppression and EC/CM co-treatment increased gut microbiota alpha diversity. Immunosuppression promoted anaerobes, such as Faecalibacterium, Streptococcus, Anaerovibrio and Dialister, and altered amino acid metabolism and nucleosides/nucleotides biosynthesis in host plasma. EC + CM cotreatment favors Phascolarctobacterium, Fusicatenibacter, Erysipelotrichaceae UCG-006, Veillonella and Mailhella. Remarkably, gut microbiota of the EC/CM co-treatment group resembled that of the pre-injury group, and the NHPs exhibited a metabolic shift towards amino acid and fatty acid/lipid biosynthesis in plasma following cell therapy. The interplay between shift in microbial community and host homeostasis during treatment suggests gut microbiome modulation could improve cell therapy outcomes.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"2"},"PeriodicalIF":6.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985617","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

Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity. 药理或遗传抑制LTCC通过抑制钙调磷酸酶活性促进心肌细胞增殖。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2025-01-11 DOI: 10.1038/s41536-025-00389-z

Lynn A C Devilée, Abou Bakr M Salama, Jessica M Miller, Janice D Reid, Qinghui Ou, Nourhan M Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K Rosengart, Douglas Andres, Jonathan Satin, Tamer M A Mohamed, James E Hudson, Riham R E Abouleisa

{"title":"Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity.","authors":"Lynn A C Devilée, Abou Bakr M Salama, Jessica M Miller, Janice D Reid, Qinghui Ou, Nourhan M Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K Rosengart, Douglas Andres, Jonathan Satin, Tamer M A Mohamed, James E Hudson, Riham R E Abouleisa","doi":"10.1038/s41536-025-00389-z","DOIUrl":"10.1038/s41536-025-00389-z","url":null,"abstract":"Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle activity in vitro, in human cardiac slices, and in vivo. Mechanistically, LTCC inhibition by RRAD or nifedipine induced CM cell cycle by modulating calcineurin activity. Moreover, ectopic expression of RRAD/CDK4/CCND in combination induced CM proliferation in vitro and in vivo, improved cardiac function and reduced scar size post-myocardial infarction.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"1"},"PeriodicalIF":6.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973288","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

Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte-myofibroblast transition in epidural fibrosis. 巨噬细胞衍生的细胞外囊泡将线粒体转移到脂肪细胞，并促进硬膜外纤维化中脂肪细胞-肌成纤维细胞的转化。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-12-30 DOI: 10.1038/s41536-024-00388-6

Feng Hua, Jinpeng Sun, Mohan Shi, Rui Mei, Zeyuan Song, Jun Liu, Mingshun Zhang

引用次数: 0

Transplantation of derivative retinal organoids from chemically induced pluripotent stem cells restored visual function. 化学诱导的多能干细胞衍生视网膜类器官移植可恢复视觉功能。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-12-27 DOI: 10.1038/s41536-024-00387-7

Ning Zhao, Chang-Jun Zhang, Xiao Zhang, Wen Wang, Kangxin Jin, Zi-Bing Jin

{"title":"Transplantation of derivative retinal organoids from chemically induced pluripotent stem cells restored visual function.","authors":"Ning Zhao, Chang-Jun Zhang, Xiao Zhang, Wen Wang, Kangxin Jin, Zi-Bing Jin","doi":"10.1038/s41536-024-00387-7","DOIUrl":"10.1038/s41536-024-00387-7","url":null,"abstract":"As an emerging type of pluripotent stem cells, chemically induced pluripotent stem cells (CiPSCs) avoid the risks of genomic disintegration by exogenous DNAs from viruses or plasmids, providing a safer stem cell source. To verify CiPSCs' capacity to differentiate into retinal organoids (ROs), we induced CiPSCs from mouse embryonic fibroblasts by defined small-molecule compounds and successfully differentiated the CiPSCs into three-dimensional ROs, in which all major retinal cell types and retinal genes were in concordance with those in vivo. We transplanted retinal photoreceptors from ROs into the subretinal space of retinal degeneration mouse models and the cells could integrate into the host retina, establish synaptic connections, and significantly improve the visual functions of the murine models. This proof-of-concept study for the first time demonstrated that CiPSCs could differentiate into ROs with a full spectrum of retinal cell types, and provided new insights into chemical approach-based retinal regeneration for degenerative diseases.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"42"},"PeriodicalIF":6.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900444","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