npj Regenerative Medicine最新文献

Stroke-induced neuroplasticity in spiny mice in the absence of tissue regeneration.

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-12-20 DOI: 10.1038/s41536-024-00386-8

Benjamin M Kidd, Justin A Varholick, Dana M Tuyn, Pradip K Kamat, Zachary D Simon, Lei Liu, Mackenzie P Mekler, Marjory Pompilus, Jodi L Bubenik, Mackenzie L Davenport, Helmut A Carter, Matteo M Grudny, W Brad Barbazuk, Sylvain Doré, Marcelo Febo, Eduardo Candelario-Jalil, Malcolm Maden, Maurice S Swanson

{"title":"Stroke-induced neuroplasticity in spiny mice in the absence of tissue regeneration.","authors":"Benjamin M Kidd, Justin A Varholick, Dana M Tuyn, Pradip K Kamat, Zachary D Simon, Lei Liu, Mackenzie P Mekler, Marjory Pompilus, Jodi L Bubenik, Mackenzie L Davenport, Helmut A Carter, Matteo M Grudny, W Brad Barbazuk, Sylvain Doré, Marcelo Febo, Eduardo Candelario-Jalil, Malcolm Maden, Maurice S Swanson","doi":"10.1038/s41536-024-00386-8","DOIUrl":"https://doi.org/10.1038/s41536-024-00386-8","url":null,"abstract":"Stroke is a major cause of disability for adults over 40 years of age. While research into animal models has prioritized treatments aimed at diminishing post-stroke damage, no studies have investigated the response to a severe stroke injury in a highly regenerative adult mammal. Here we investigate the effects of transient ischemia on adult spiny mice, Acomys cahirinus, due to their ability to regenerate multiple tissues without scarring. Transient middle cerebral artery occlusion was performed and Acomys showed rapid behavioral recovery post-stroke yet failed to regenerate impacted brain regions. An Acomys brain atlas in combination with functional (f)MRI demonstrated recovery coincides with neuroplasticity. The strength and quality of the global connectome are preserved post-injury with distinct contralateral and ipsilateral brain regions compensating for lost tissue. Thus, we propose Acomys recovers functionally from an ischemic stroke injury not by tissue regeneration but by altering its brain connectome.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"41"},"PeriodicalIF":6.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873341","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

Cardiomyocyte proliferation and heart regeneration in adult Xenopus tropicalis evidenced by a transgenic reporter line.

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-12-19 DOI: 10.1038/s41536-024-00384-w

Xiao-Lin Lin, Jin-Hua Lin, Yan Cao, Han Zhang, Si-Yi He, Hai-Yan Wu, Ze-Bing Ye, Li Zheng, Xu-Feng Qi

{"title":"Cardiomyocyte proliferation and heart regeneration in adult Xenopus tropicalis evidenced by a transgenic reporter line.","authors":"Xiao-Lin Lin, Jin-Hua Lin, Yan Cao, Han Zhang, Si-Yi He, Hai-Yan Wu, Ze-Bing Ye, Li Zheng, Xu-Feng Qi","doi":"10.1038/s41536-024-00384-w","DOIUrl":"https://doi.org/10.1038/s41536-024-00384-w","url":null,"abstract":"Cardiomyocyte proliferation in adult Xenopus tropicalis during heart regeneration has remained largely contentious due to the absence of genetic evidence. Here, we generated a transgenic reporter line Tg(mlc2:H2C) expressing mCherry specifically in cardiomyocyte nuclei driven by the promoter of myosin light chain 2 (mlc2). Using the reporter line, we found that traditional whole-cell staining is not a rigorous way to identify cardiomyocytes in adult Xenopus tropicalis when using a cryosection with common thickness (5 μm) which leading to a high error, but this deviation could be reduced by increasing section thickness. In addition, the reporter line confirmed that apex resection injury greatly increased the proliferation of mlc2+ cardiomyocytes at 3-30 days post-resection (dpr), thereby regenerating the lost cardiac muscle by 30 dpr in adult Xenopus tropicalis. Our findings from the reporter line have rigorously defined cardiomyocyte proliferation in adult heart upon injury, thereby contributing heart regeneration in adult Xenopus tropicalis.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"40"},"PeriodicalIF":6.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866455","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

Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury.

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-12-19 DOI: 10.1038/s41536-024-00383-x

Nandaraj Taye, Levon Rodriguez, James C Iatridis, Woojin M Han, Dirk Hubmacher

引用次数: 0

Early resistance rehabilitation improves functional regeneration following segmental bone defect injury. 早期阻力康复可改善节段性骨缺损损伤后的功能再生。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-12-12 DOI: 10.1038/s41536-024-00377-9

Kylie E Williams, Julia Andraca Harrer, Steven A LaBelle, Kelly Leguineche, Jarred Kaiser, Salil Karipott, Angela Lin, Alyssa Vongphachanh, Travis Fulton, J Walker Rosenthal, Farhan Muhib, Keat Ghee Ong, Jeffrey A Weiss, Nick J Willett, Robert E Guldberg

{"title":"Early resistance rehabilitation improves functional regeneration following segmental bone defect injury.","authors":"Kylie E Williams, Julia Andraca Harrer, Steven A LaBelle, Kelly Leguineche, Jarred Kaiser, Salil Karipott, Angela Lin, Alyssa Vongphachanh, Travis Fulton, J Walker Rosenthal, Farhan Muhib, Keat Ghee Ong, Jeffrey A Weiss, Nick J Willett, Robert E Guldberg","doi":"10.1038/s41536-024-00377-9","DOIUrl":"10.1038/s41536-024-00377-9","url":null,"abstract":"Many studies have explored different loading and rehabilitation strategies, yet rehabilitation intensity and its impact on the local strain environment and bone healing have largely not been investigated. This study combined implantable strain sensors and subject-specific finite element models in a 2 mm rodent segmental bone defect model. After injury animals were underwent high or low intensity rehabilitation. High intensity rehabilitation increased local strains within the regenerative niche by an average of 44% compared to the low intensity rehabilitation. Finite element modeling demonstrated that resistance rehabilitation significantly increased compressive strain by a factor of 2.0 at week 2 and 4.45 after 4 weeks of rehabilitation. Animals that underwent resistance running had the greatest bone volume and improved functional recovery with regenerated femurs that matched intact failure torque and torsional stiffness values. These results demonstrate the potential for early resistance rehabilitation to improve bone healing.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"38"},"PeriodicalIF":6.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820085","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

Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs.

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-12-10 DOI: 10.1038/s41536-024-00380-0

Jing Li, Pia Balmaceda, Thuy Ha, Joseph R Visker, Nicole Maalouf, Eugene Kwan, Guillaume L Hoareau, Michel Accad, Ravi Ranjan, Craig H Selzman, Stavros G Drakos, Robin M Shaw, TingTing Hong

{"title":"Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs.","authors":"Jing Li, Pia Balmaceda, Thuy Ha, Joseph R Visker, Nicole Maalouf, Eugene Kwan, Guillaume L Hoareau, Michel Accad, Ravi Ranjan, Craig H Selzman, Stavros G Drakos, Robin M Shaw, TingTing Hong","doi":"10.1038/s41536-024-00380-0","DOIUrl":"10.1038/s41536-024-00380-0","url":null,"abstract":"Heart failure (HF) is a major cause of mortality and morbidity worldwide, yet with limited therapeutic options. Cardiac bridging integrator 1 (cBIN1), a cardiomyocyte transverse-tubule (t-tubule) scaffolding protein which organizes the calcium handling machinery, is transcriptionally reduced in HF and can be recovered for functional rescue in mice. Here we report that in human patients with HF with reduced ejection fraction (HFrEF), left ventricular cBIN1 levels linearly correlate with organ-level ventricular remodeling such as diastolic diameter. Using a minipig model of right ventricular tachypacing-induced non-ischemic dilated cardiomyopathy and chronic HFrEF, we identified that a single intravenous low dose (6 × 1011 vg/kg) of adeno associated virus 9 (AAV9)-packaged cBIN1 improves ventricular remodeling and performance, reduces pulmonary and systemic fluid retention, and increases survival in HFrEF minipigs. In cardiomyocytes, AAV9-cBIN1 restores t-tubule organization and ultrastructure in failing cardiomyocytes. In conclusion, AAV9-based cBIN1 gene therapy rescues non-ischemic HFrEF with reduced mortality in minipigs.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"36"},"PeriodicalIF":6.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808610","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

Attenuation of skin injury by a MARCO targeting PLGA nanoparticle.

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-12-06 DOI: 10.1038/s41536-024-00381-z

Ummiye V Onay, Dan Xu, Dauren Biyashev, Spencer T Evans, Michael M Demczuk, Tobias Neef, Joseph R Podojil, Sara Beddow, Nathan C Gianneschi, I Caroline Le Poole, Stephen D Miller, Kurt Q Lu

{"title":"Attenuation of skin injury by a MARCO targeting PLGA nanoparticle.","authors":"Ummiye V Onay, Dan Xu, Dauren Biyashev, Spencer T Evans, Michael M Demczuk, Tobias Neef, Joseph R Podojil, Sara Beddow, Nathan C Gianneschi, I Caroline Le Poole, Stephen D Miller, Kurt Q Lu","doi":"10.1038/s41536-024-00381-z","DOIUrl":"10.1038/s41536-024-00381-z","url":null,"abstract":"Cutaneous exposure to the DNA alkylating class of chemotherapeutic agents including nitrogen mustard (NM) leads to both skin injury and systemic inflammation. Circulating myeloid subsets recruited to the skin act to further exacerbate local tissue damage while interfering with the wound healing process. We demonstrate herein that intravenous delivery of poly(lactic-co-glycolic acid) immune-modifying nanoparticles (PLGA-IMPs) shortly after NM exposure restricts accumulation of macrophages and inflammatory monocytes at the injury site, resulting in attenuated skin pathology. Furthermore, PLGA-IMPs induce an early influx and local enrichment of Foxp3+ regulatory T cells (Treg) in the skin lesions critical for the suppression of myeloid cell-pro-inflammatory responses via induction of IL-10 and TGF-β in the cutaneous milieu. Functional depletion of CD4+ Tregs ablates the efficacy of PLGA-IMPs accompanied by a loss of local accumulation of anti-inflammatory cytokines essential for wound healing. Thus, in severe skin trauma, PLGA-IMPs may have therapeutic potential via modulation of inflammatory myeloid cells and regulatory T lymphocytes.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"37"},"PeriodicalIF":6.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787915","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

Peripheral nerve-derived CSF1 induces BMP2 expression in macrophages to promote nerve regeneration and wound healing. 外周神经源性 CSF1 可诱导巨噬细胞表达 BMP2，从而促进神经再生和伤口愈合。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-11-21 DOI: 10.1038/s41536-024-00379-7

Kai Wang, Binyu Song, Yuhan Zhu, Juanli Dang, Tong Wang, Yajuan Song, Yi Shi, Shuang You, Sijia Li, Zhou Yu, Baoqiang Song

{"title":"Peripheral nerve-derived CSF1 induces BMP2 expression in macrophages to promote nerve regeneration and wound healing.","authors":"Kai Wang, Binyu Song, Yuhan Zhu, Juanli Dang, Tong Wang, Yajuan Song, Yi Shi, Shuang You, Sijia Li, Zhou Yu, Baoqiang Song","doi":"10.1038/s41536-024-00379-7","DOIUrl":"10.1038/s41536-024-00379-7","url":null,"abstract":"The precise mechanisms regulating inflammatory and prorepair macrophages have not been fully elucidated, despite the pivotal role played by innate immunity in wound healing. We first employed a denervation wound model to validate the crosstalk between neurons and macrophages. Compared to normal wound healing, the denervation wound healing process involved fewer macrophages, decreased angiogenesis, and delayed wound healing. Consistent with the results of the scRNA-seq libraries, the number of early-phase wound proinflammatory and late-phase wound prorepair macrophages were decreased during the denervation wound healing process. We profiled early-phase and late-phase skin wounds in mice at the transcriptional and functional levels and compared them to those of normal wounds. We revealed a neuroimmune regulatory pathway driven by peripheral nerve-derived CSF1 that induces BMP2 expression in prorepair macrophages and enhances nerve regeneration. Crosstalk between neurons and macrophages facilitates the healing process of wounds and provides a potential strategy for wound healing therapy.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"35"},"PeriodicalIF":6.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689732","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

Heart regeneration from the whole-organism perspective to single-cell resolution. 从整个生物体角度到单细胞分辨率的心脏再生。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-11-15 DOI: 10.1038/s41536-024-00378-8

Xiaoxin Chen, Xiaochen Zhong, Guo N Huang

引用次数: 0

Systemic and local lipid adaptations underlie regeneration in Drosophila melanogaster and Ambystoma mexicanum. 黑腹果蝇和墨西哥巨蜥再生的系统和局部脂质适应性基础

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-10-29 DOI: 10.1038/s41536-024-00375-x

Ines C Kübler, Jenny Kretzschmar, Maria Nieves Arredondo-Lasso, Sean D Keeley, Luca Claudia Rößler, Katharina Ganss, Tatiana Sandoval-Guzmán, Marko Brankatschk

{"title":"Systemic and local lipid adaptations underlie regeneration in Drosophila melanogaster and Ambystoma mexicanum.","authors":"Ines C Kübler, Jenny Kretzschmar, Maria Nieves Arredondo-Lasso, Sean D Keeley, Luca Claudia Rößler, Katharina Ganss, Tatiana Sandoval-Guzmán, Marko Brankatschk","doi":"10.1038/s41536-024-00375-x","DOIUrl":"10.1038/s41536-024-00375-x","url":null,"abstract":"In regenerating tissues, synthesis and remodeling of membranes rely on lipid turnover and transport. Our study addresses lipid adaptations in intestinal regeneration of Drosophila melanogaster and limb regeneration of Ambystoma mexicanum. We found changes in lipid profiles at different locations: transport, storage organs and regenerating tissues. We demonstrate that attenuating insulin signaling, exclusively in fat storage, inhibits the regeneration-specific response in both the fat storage and the regenerating tissue in Drosophila. Furthermore, in uninjured axolotls we found sex-specific lipid profiles in both storage and circulation, while in regenerating animals these differences subside. The regenerating limb presents a unique sterol profile, albeit with no sex differences. We postulate that regeneration triggers a systemic response, where organs storing lipids play a significant role in the regulation of systemic lipid traffic. Second, that this response may be an active and well-regulated mechanism, as observed when homeostatic sex-differences disappear in regenerating salamanders.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"33"},"PeriodicalIF":6.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548922","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

Regeneration-specific promoter switching facilitates Mest expression in the mouse digit tip to modulate neutrophil response. 再生特异性启动子转换促进了小鼠指尖Mest的表达，从而调节中性粒细胞的反应。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-10-28 DOI: 10.1038/s41536-024-00376-w

Vivian Jou, Sophia M Peña, Jessica A Lehoczky

{"title":"Regeneration-specific promoter switching facilitates Mest expression in the mouse digit tip to modulate neutrophil response.","authors":"Vivian Jou, Sophia M Peña, Jessica A Lehoczky","doi":"10.1038/s41536-024-00376-w","DOIUrl":"10.1038/s41536-024-00376-w","url":null,"abstract":"The mouse digit tip regenerates following amputation, a process mediated by a cellularly heterogeneous blastema. We previously found the gene Mest to be highly expressed in mesenchymal cells of the blastema and a strong candidate pro-regenerative gene. We now show Mest digit expression is regeneration-specific and not upregulated in post-amputation fibrosing proximal digits. Mest homozygous knockout mice exhibit delayed bone regeneration though no phenotype is found in paternal knockout mice, inconsistent with the defined maternal genomic imprinting of Mest. We demonstrate that promoter switching, not loss of imprinting, regulates biallelic Mest expression in the blastema and does not occur during embryogenesis, indicating a regeneration-specific mechanism. Requirement for Mest expression is tied to modulating neutrophil response, as revealed by scRNAseq and FACS comparing wildtype and knockout blastemas. Collectively, the imprinted gene Mest is required for proper digit tip regeneration and its blastema expression is facilitated by promoter switching for biallelic expression.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"32"},"PeriodicalIF":6.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523616","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