npj Regenerative Medicine最新文献_第2页

Integrative cartilage repair using acellular allografts for engineered structure and surface lubrication in vivo. 利用细胞异体移植物进行体内软骨结构和表面润滑的综合修复。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-09-28 DOI: 10.1038/s41536-024-00367-x

Jeanne E Barthold, Luyao Cai, Kaitlin P McCreery, Kristine M Fischenich, Kevin N Eckstein, Virginia L Ferguson, Nancy C Emery, Gert Breur, Corey P Neu

{"title":"Integrative cartilage repair using acellular allografts for engineered structure and surface lubrication in vivo.","authors":"Jeanne E Barthold, Luyao Cai, Kaitlin P McCreery, Kristine M Fischenich, Kevin N Eckstein, Virginia L Ferguson, Nancy C Emery, Gert Breur, Corey P Neu","doi":"10.1038/s41536-024-00367-x","DOIUrl":"https://doi.org/10.1038/s41536-024-00367-x","url":null,"abstract":"The repair of articular cartilage after damage is challenging, and decellularized tissue offers a possible treatment option to promote regeneration. Here, we show that acellular osteochondral allografts improve integrative cartilage repair compared to untreated defects after 6 months in an ovine model. Functional measures of intratissue strain/structure assessed by MRI demonstrate similar biomechanics of implants and native cartilage. Compared to native tissue and defects, the structure, composition, and tribology of acellular allografts preserve surface roughness and lubrication, material properties under compression and relaxation, compositional ratios of collagen:glycosaminoglycan and collagen:phosphate, and relative composition of types I/II collagen. While high cellularity was observed in bone regions and integration zones between cartilage-allografts, recellularization of chondral implants was inconsistent, with cell migration typically less than ~750 µm into the dense decellularized tissue, possibly limiting long-term cellular maintenance. Our results demonstrate the structural and biomechanical efficacy of acellular allografts for at least six months in vivo.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"25"},"PeriodicalIF":6.4,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332261","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

Implication of CXCR2-Src axis in the angiogenic and osteogenic effects of FP-TEB. CXCR2-Src轴在FP-TEB的血管生成和成骨效应中的作用。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-09-20 DOI: 10.1038/s41536-024-00364-0

Sihao He, Tianyong Hou, Jiangling Zhou, Bo Yu, Juan Cai, Fei Luo, Jianzhong Xu, Junchao Xing

引用次数: 0

Calorie restriction and rapamycin distinctly restore non-canonical ORF translation in the muscles of aging mice 卡路里限制和雷帕霉素可明显恢复衰老小鼠肌肉中的非规范 ORF 翻译

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-09-19 DOI: 10.1038/s41536-024-00369-9

Nitish Mittal, Meric Ataman, Lionel Tintignac, Daniel J. Ham, Lena Jörin, Alexander Schmidt, Michael Sinnreich, Markus A. Ruegg, Mihaela Zavolan

{"title":"Calorie restriction and rapamycin distinctly restore non-canonical ORF translation in the muscles of aging mice","authors":"Nitish Mittal, Meric Ataman, Lionel Tintignac, Daniel J. Ham, Lena Jörin, Alexander Schmidt, Michael Sinnreich, Markus A. Ruegg, Mihaela Zavolan","doi":"10.1038/s41536-024-00369-9","DOIUrl":"https://doi.org/10.1038/s41536-024-00369-9","url":null,"abstract":"Loss of protein homeostasis is one of the hallmarks of aging. As such, interventions that restore proteostasis should slow down the aging process and improve healthspan. Two of the most broadly used anti-aging interventions that are effective in organisms from yeast to mammals are calorie restriction (CR) and rapamycin (RM) treatment. To identify the regulatory mechanisms by which these interventions improve the protein homeostasis, we carried out ribosome footprinting in the muscle of mice aged under standard conditions, or under long-term treatment with CR or RM. We found that the treatments distinctly impact the non-canonical translation, RM primarily remodeling the translation of upstream open reading frames (uORFs), while CR restores stop codon readthrough and the translation of downstream ORFs. Proteomics analysis revealed the expression of numerous non-canonical ORFs at the protein level. The corresponding peptides may provide entry points for therapies aiming to maintain muscle function and extend health span.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"4 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263061","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

Multifunctional injectable microspheres for osteoarthritis therapy via spatiotemporally modulating macrophage polarization and inflammation 通过时空调节巨噬细胞极化和炎症，用于骨关节炎治疗的多功能注射微球

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-09-17 DOI: 10.1038/s41536-024-00368-w

Shengnan Qiu, Yanbin Shi, Hengchang Zang, Xiaochen Sun, Qingjie Wang, Xianglei Fu, Hua Shen, Fanyang Mo, Yankun Zhang, Xiangqin Chen, Jiamin Zhou, Lian Li, Guimei Lin

{"title":"Multifunctional injectable microspheres for osteoarthritis therapy via spatiotemporally modulating macrophage polarization and inflammation","authors":"Shengnan Qiu, Yanbin Shi, Hengchang Zang, Xiaochen Sun, Qingjie Wang, Xianglei Fu, Hua Shen, Fanyang Mo, Yankun Zhang, Xiangqin Chen, Jiamin Zhou, Lian Li, Guimei Lin","doi":"10.1038/s41536-024-00368-w","DOIUrl":"https://doi.org/10.1038/s41536-024-00368-w","url":null,"abstract":"Local injection of anti-inflammatory drugs for osteoarthritis emerged as a promising administration in the clinic, and sustained-release dosage forms have great potential for future therapeutic applications. Controlling the response of patients only in the acute inflammatory phase is currently the focus of therapeutic interventions. To relieve acute pain in patients and to improve the long-term prognosis effect of osteoarthritis treatment, we designed a two-pronged approach in this research: an injectable double-layer microsphere containing a “nonsteroidal anti-inflammatory drug - macrophage polarizing factor” was constructed. The results indicated that microspheres could regulate the intra-articular environment by inhibiting local inflammatory cytokine production, promoting macrophage polarization to the M2-phenotype, and increasing the expression of cartilage repair factors. Polymers chosen could govern the biocompatibility of microspheres and control the release sequence of the two drugs. Injection of microspheres into the degenerative articular cavity of rats leads to suppressed inflammation and well-promoted cartilage regeneration.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"16 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263062","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

Leiomodin 2 neonatal dilated cardiomyopathy mutation results in altered actin gene signatures and cardiomyocyte dysfunction Leiomodin 2 基因突变导致新生儿扩张型心肌病肌动蛋白基因特征改变和心肌细胞功能障碍

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-09-16 DOI: 10.1038/s41536-024-00366-y

Jessika B. Iwanski, Christopher T. Pappas, Rachel M. Mayfield, Gerrie P. Farman, Rebecca Ahrens-Nicklas, Jared M. Churko, Carol C. Gregorio

{"title":"Leiomodin 2 neonatal dilated cardiomyopathy mutation results in altered actin gene signatures and cardiomyocyte dysfunction","authors":"Jessika B. Iwanski, Christopher T. Pappas, Rachel M. Mayfield, Gerrie P. Farman, Rebecca Ahrens-Nicklas, Jared M. Churko, Carol C. Gregorio","doi":"10.1038/s41536-024-00366-y","DOIUrl":"https://doi.org/10.1038/s41536-024-00366-y","url":null,"abstract":"Neonatal dilated cardiomyopathy (DCM) is a poorly understood muscular disease of the heart. Several homozygous biallelic variants in LMOD2, the gene encoding the actin-binding protein Leiomodin 2, have been identified to result in severe DCM. Collectively, LMOD2-related cardiomyopathies present with cardiac dilation and decreased heart contractility, often resulting in neonatal death. Thus, it is evident that Lmod2 is essential to normal human cardiac muscle function. This study aimed to understand the underlying pathophysiology and signaling pathways related to the first reported LMOD2 variant (c.1193 G > A, p.Trp398*). Using patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a mouse model harboring the homologous mutation to the patient, we discovered dysregulated actin-thin filament lengths, altered contractility and calcium handling properties, as well as alterations in the serum response factor (SRF)-dependent signaling pathway. These findings reveal that LMOD2 may be regulating SRF activity in an actin-dependent manner and provide a potential new strategy for the development of biologically active molecules to target LMOD2-related cardiomyopathies.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263063","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

Role of umbilical cord mesenchymal stromal cells in skin rejuvenation. 脐带间充质基质细胞在皮肤年轻化中的作用。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-05-10 DOI: 10.1038/s41536-024-00363-1

Le Chang, Wei-Wen Fan, He-Ling Yuan, Xin Liu, Qiang Wang, Guang-Ping Ruan, Xing-Hua Pan, Xiang-Qing Zhu

{"title":"Role of umbilical cord mesenchymal stromal cells in skin rejuvenation.","authors":"Le Chang, Wei-Wen Fan, He-Ling Yuan, Xin Liu, Qiang Wang, Guang-Ping Ruan, Xing-Hua Pan, Xiang-Qing Zhu","doi":"10.1038/s41536-024-00363-1","DOIUrl":"10.1038/s41536-024-00363-1","url":null,"abstract":"Aging is the main cause of many degenerative diseases. The skin is the largest and the most intuitive organ that reflects the aging of the body. Under the interaction of endogenous and exogenous factors, there are cumulative changes in the structure, function, and appearance of the skin, which are characterized by decreased synthesis of collagen and elastin, increased wrinkles, relaxation, pigmentation, and other aging characteristics. skin aging is inevitable, but it can be delayed. The successful isolation of mesenchymal stromal cells (MSC) in 1991 has greatly promoted the progress of cell therapy in human diseases. The International Society for Cellular Therapy (ISCT) points out that the MSC is a kind of pluripotent progenitor cells that have self-renewal ability (limited) in vitro and the potential for mesenchymal cell differentiation. This review mainly introduces the role of perinatal umbilical cord-derived MSC(UC-MSC) in the field of skin rejuvenation. An in-depth and systematic understanding of the mechanism of UC-MSCs against skin aging is of great significance for the early realization of the clinical transformation of UC-MSCs. This paper summarized the characteristics of skin aging and summarized the mechanism of UC-MSCs in skin rejuvenation reported in recent years. In order to provide a reference for further research of UC-MSCs to delay skin aging.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"20"},"PeriodicalIF":7.2,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905187","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

Exploiting in silico modelling to enhance translation of liver cell therapies from bench to bedside. 利用硅学建模促进肝细胞疗法从实验室到临床的转化。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-05-09 DOI: 10.1038/s41536-024-00361-3

Candice Ashmore-Harris, Evangelia Antonopoulou, Simon M Finney, Melissa R Vieira, Matthew G Hennessy, Andreas Muench, Wei-Yu Lu, Victoria L Gadd, Alicia J El Haj, Stuart J Forbes, Sarah L Waters

{"title":"Exploiting in silico modelling to enhance translation of liver cell therapies from bench to bedside.","authors":"Candice Ashmore-Harris, Evangelia Antonopoulou, Simon M Finney, Melissa R Vieira, Matthew G Hennessy, Andreas Muench, Wei-Yu Lu, Victoria L Gadd, Alicia J El Haj, Stuart J Forbes, Sarah L Waters","doi":"10.1038/s41536-024-00361-3","DOIUrl":"10.1038/s41536-024-00361-3","url":null,"abstract":"Cell therapies are emerging as promising treatments for a range of liver diseases but translational bottlenecks still remain including: securing and assessing the safe and effective delivery of cells to the disease site; ensuring successful cell engraftment and function; and preventing immunogenic responses. Here we highlight three therapies, each utilising a different cell type, at different stages in their clinical translation journey: transplantation of multipotent mesenchymal stromal/signalling cells, hepatocytes and macrophages. To overcome bottlenecks impeding clinical progression, we advocate for wider use of mechanistic in silico modelling approaches. We discuss how in silico approaches, alongside complementary experimental approaches, can enhance our understanding of the mechanisms underlying successful cell delivery and engraftment. Furthermore, such combined theoretical-experimental approaches can be exploited to develop novel therapies, address safety and efficacy challenges, bridge the gap between in vitro and in vivo model systems, and compensate for the inherent differences between animal model systems and humans. We also highlight how in silico model development can result in fewer and more targeted in vivo experiments, thereby reducing preclinical costs and experimental animal numbers and potentially accelerating translation to the clinic. The development of biologically-accurate in silico models that capture the mechanisms underpinning the behaviour of these complex systems must be reinforced by quantitative methods to assess cell survival post-transplant, and we argue that non-invasive in vivo imaging strategies should be routinely integrated into transplant studies.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"19"},"PeriodicalIF":7.2,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11081951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900219","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

Structural, angiogenic, and immune responses influencing myocardial regeneration: a glimpse into the crucible 影响心肌再生的结构、血管生成和免疫反应：熔炉一瞥

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-04-30 DOI: 10.1038/s41536-024-00357-z

Basil M. Baccouche, Stefan Elde, Hanjay Wang, Y. Joseph Woo

引用次数: 0

Epigenetic mechanisms regulate sex differences in cardiac reparative functions of bone marrow progenitor cells 表观遗传机制调控骨髓祖细胞心脏修复功能的性别差异

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-04-29 DOI: 10.1038/s41536-024-00362-2

Charan Thej, Rajika Roy, Zhongjian Cheng, Venkata Naga Srikanth Garikipati, May M. Truongcao, Darukeshwara Joladarashi, Vandana Mallaredy, Maria Cimini, Carolina Gonzalez, Ajit Magadum, Jayashri Ghosh, Cindy Benedict, Walter J. Koch, Raj Kishore

{"title":"Epigenetic mechanisms regulate sex differences in cardiac reparative functions of bone marrow progenitor cells","authors":"Charan Thej, Rajika Roy, Zhongjian Cheng, Venkata Naga Srikanth Garikipati, May M. Truongcao, Darukeshwara Joladarashi, Vandana Mallaredy, Maria Cimini, Carolina Gonzalez, Ajit Magadum, Jayashri Ghosh, Cindy Benedict, Walter J. Koch, Raj Kishore","doi":"10.1038/s41536-024-00362-2","DOIUrl":"https://doi.org/10.1038/s41536-024-00362-2","url":null,"abstract":"Historically, a lower incidence of cardiovascular diseases (CVD) and related deaths in women as compared with men of the same age has been attributed to female sex hormones, particularly estrogen and its receptors. Autologous bone marrow stem cell (BMSC) clinical trials for cardiac cell therapy overwhelmingly included male patients. However, meta-analysis data from these trials suggest a better functional outcome in postmenopausal women as compared with aged-matched men. Mechanisms governing sex-specific cardiac reparative activity in BMSCs, with and without the influence of sex hormones, remain unexplored. To discover these mechanisms, Male (M), female (F), and ovariectomized female (OVX) mice-derived EPCs were subjected to a series of molecular and epigenetic analyses followed by in vivo functional assessments of cardiac repair. F-EPCs and OVX EPCs show a lower inflammatory profile and promote enhanced cardiac reparative activity after intra-cardiac injections in a male mouse model of myocardial infarction (MI). Epigenetic sequencing revealed a marked difference in the occupancy of the gene repressive H3K9me3 mark, particularly at transcription start sites of key angiogenic and proinflammatory genes in M-EPCs compared with F-EPCs and OVX-EPCs. Our study unveiled that functional sex differences in EPCs are, in part, mediated by differential epigenetic regulation of the proinflammatory and anti-angiogenic gene CCL3, orchestrated by the control of H3K9me3 by histone methyltransferase, G9a/Ehmt2. Our research highlights the importance of considering the sex of donor cells for progenitor-based tissue repair.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"30 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837495","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

The adult environment promotes the transcriptional maturation of human iPSC-derived muscle grafts 成人环境促进人类 iPSC 衍生肌肉移植物的转录成熟

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-04-04 DOI: 10.1038/s41536-024-00360-4

Sarah B. Crist, Karim Azzag, James Kiley, Ilsa Coleman, Alessandro Magli, Rita C. R. Perlingeiro

{"title":"The adult environment promotes the transcriptional maturation of human iPSC-derived muscle grafts","authors":"Sarah B. Crist, Karim Azzag, James Kiley, Ilsa Coleman, Alessandro Magli, Rita C. R. Perlingeiro","doi":"10.1038/s41536-024-00360-4","DOIUrl":"https://doi.org/10.1038/s41536-024-00360-4","url":null,"abstract":"Pluripotent stem cell (PSC)-based cell therapy is an attractive option for the treatment of multiple human disorders, including muscular dystrophies. While in vitro differentiating PSCs can generate large numbers of human lineage-specific tissue, multiple studies evidenced that these cell populations mostly display embryonic/fetal features. We previously demonstrated that transplantation of PSC-derived myogenic progenitors provides long-term engraftment and functional improvement in several dystrophic mouse models, but it remained unknown whether donor-derived myofibers mature to match adult tissue. Here, we transplanted iPAX7 myogenic progenitors into muscles of non-dystrophic and dystrophic mice and compared the transcriptional landscape of human grafts with respective in vitro-differentiated iPAX7 myotubes as well as human skeletal muscle biospecimens. Pairing bulk RNA sequencing with computational deconvolution of human reads, we were able to pinpoint key myogenic changes that occur during the in vitro–to–in vivo transition, confirm developmental maturity, and consequently evaluate their applicability for cell-based therapies.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"105 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579619","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