npj Regenerative Medicine最新文献

{"title":"Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria.","authors":"Deping Wang, Bowen Li, Shuchao Wang, Yingjian Hao, Hua Wang, Wei Sun, Jimin Cao, Xin Zhou, Bin Zheng","doi":"10.1038/s41536-023-00315-1","DOIUrl":"10.1038/s41536-023-00315-1","url":null,"abstract":"<p><p>Mitochondrial dysfunction and subsequent accumulation of reactive oxygen species (ROS) are key contributors to the pathology of ischemic cerebrovascular disease. Therefore, elimination of ROS and damaged mitochondria is crucial for the effective treatment of this disease. For this purpose, we designed an inhalation nanotherapeutic agent, P/D@Mn/Co₃O₄, to treat ischemic cerebrovascular disease. Mn/Co₃O₄ effectively removed excess ROS from cells, reduced acute cellular oxidative stress, and protected neural cells from apoptosis. Furthermore, it depleted the H⁺ surrounding mitochondria and depolarized the mitochondrial membrane potential, inducing mitophagy and eliminating abnormal mitochondria, thereby avoiding the continuous overproduction of ROS by eliminating the source of ROS regeneration. On intranasal administration, Mn/Co₃O₄ encapsulated by platelet membranes and 2,3-(dioxy propyl)-trimethylammonium chloride can bypass the blood-brain barrier, enter the brain through the trigeminal and olfactory pathways, and target inflammatory regions to remove ROS and damaged mitochondria from the lesion area. In rat models of stroke and vascular dementia, P/D@Mn/Co₃O₄ effectively inhibited the symptoms of acute and chronic cerebral ischemia by scavenging ROS and damaged mitochondria in the affected area. Our findings indicate that the nanotherapeutic agent developed in this study can be used for the effective treatment of ischemic cerebrovascular disease.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"44"},"PeriodicalIF":7.2,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10349894","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}

{"title":"Transgene-free direct conversion of murine fibroblasts into functional muscle stem cells.","authors":"Xhem Qabrati, Inseon Kim, Adhideb Ghosh, Nicola Bundschuh, Falko Noé, Andrew S Palmer, Ori Bar-Nur","doi":"10.1038/s41536-023-00317-z","DOIUrl":"10.1038/s41536-023-00317-z","url":null,"abstract":"<p><p>Transcription factor-based cellular reprogramming provides an attractive approach to produce desired cell types for regenerative medicine purposes. Such cellular conversions are widely dependent on viral vectors to efficiently deliver and express defined factors in target cells. However, use of viral vectors is associated with unfavorable genomic integrations that can trigger deleterious molecular consequences, rendering this method a potential impediment to clinical applications. Here, we report on a highly efficient transgene-free approach to directly convert mouse fibroblasts into induced myogenic progenitor cells (iMPCs) by overexpression of synthetic MyoD-mRNA in concert with an enhanced small molecule cocktail. First, we performed a candidate compound screen and identified two molecules that enhance fibroblast reprogramming into iMPCs by suppression of the JNK and JAK/STAT pathways. Simultaneously, we developed an optimal transfection protocol to transiently overexpress synthetic MyoD-mRNA in fibroblasts. Combining these two techniques enabled robust and rapid reprogramming of fibroblasts into Pax7 positive iMPCs in as little as 10 days. Nascent transgene-free iMPCs proliferated extensively in vitro, expressed a suite of myogenic stem cell markers, and could differentiate into highly multinucleated and contractile myotubes. Furthermore, using global and single-cell transcriptome assays, we delineated gene expression changes associated with JNK and JAK/STAT pathway inhibition during reprogramming, and identified in iMPCs a Pax7⁺ stem cell subpopulation resembling satellite cells. Last, transgene-free iMPCs robustly engrafted skeletal muscles of a Duchenne muscular dystrophy mouse model, restoring dystrophin expression in hundreds of myofibers. In summary, this study reports on an improved and clinically safer approach to convert fibroblasts into myogenic stem cells that can efficiently contribute to muscle regeneration in vivo.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"43"},"PeriodicalIF":7.2,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10325352","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}

{"title":"Author Correction: The bright side of fibroblasts: molecular signature and regenerative cues in major organs.","authors":"Rita N Gomes, Filipa Manuel, Diana S Nascimento","doi":"10.1038/s41536-023-00319-x","DOIUrl":"10.1038/s41536-023-00319-x","url":null,"abstract":"","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"42"},"PeriodicalIF":7.2,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9965414","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}

{"title":"Functional ProTracer identifies patterns of cell proliferation in tissues and underlying regulatory mechanisms.","authors":"Xiuxiu Liu, Maoying Han, Wendong Weng, Yan Li, Wenjuan Pu, Kuo Liu, Xufeng Li, Lingjuan He, Ruilin Sun, Ruling Shen, Yulong He, Dandan Liang, Yi-Han Chen, Qing-Dong Wang, Jan S Tchorz, Bin Zhou","doi":"10.1038/s41536-023-00318-y","DOIUrl":"10.1038/s41536-023-00318-y","url":null,"abstract":"<p><p>A genetic system, ProTracer, has been recently developed to record cell proliferation in vivo. However, the ProTracer is initiated by an infrequently used recombinase Dre, which limits its broad application for functional studies employing floxed gene alleles. Here we generated Cre-activated functional ProTracer (fProTracer) mice, which enable simultaneous recording of cell proliferation and tissue-specific gene deletion, facilitating broad functional analysis of cell proliferation by any Cre driver.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"41"},"PeriodicalIF":7.2,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9946025","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}

{"title":"A postnatal network of co-hepato/pancreatic stem/progenitors in the biliary trees of pigs and humans.","authors":"Wencheng Zhang, Xicheng Wang, Giacomo Lanzoni, Eliane Wauthier, Sean Simpson, Jennifer Ashley Ezzell, Amanda Allen, Carolyn Suitt, Jonah Krolik, Alexander Jhirad, Juan Dominguez-Bendala, Vincenzo Cardinale, Domenico Alvaro, Diletta Overi, Eugenio Gaudio, Praveen Sethupathy, Guido Carpino, Christopher Adin, Jorge A Piedrahita, Kyle Mathews, Zhiying He, Lola McAdams Reid","doi":"10.1038/s41536-023-00303-5","DOIUrl":"10.1038/s41536-023-00303-5","url":null,"abstract":"<p><p>A network of co-hepato/pancreatic stem/progenitors exists in pigs and humans in Brunner's Glands in the submucosa of the duodenum, in peribiliary glands (PBGs) of intrahepatic and extrahepatic biliary trees, and in pancreatic duct glands (PDGs) of intrapancreatic biliary trees, collectively supporting hepatic and pancreatic regeneration postnatally. The network is found in humans postnatally throughout life and, so far, has been demonstrated in pigs postnatally at least through to young adulthood. These stem/progenitors in vivo in pigs are in highest numbers in Brunner's Glands and in PDGs nearest the duodenum, and in humans are in Brunner's Glands and in PBGs in the hepato/pancreatic common duct, a duct missing postnatally in pigs. Elsewhere in PDGs in pigs and in all PDGs in humans are only committed unipotent or bipotent progenitors. Stem/progenitors have genetic signatures in liver/pancreas-related RNA-seq data based on correlation, hierarchical clustering, differential gene expression and principal component analyses (PCA). Gene expression includes representative traits of pluripotency genes (SOX2, OCT4), endodermal transcription factors (e.g. SOX9, SOX17, PDX1), other stem cell traits (e.g. NCAM, CD44, sodium iodide symporter or NIS), and proliferation biomarkers (Ki67). Hepato/pancreatic multipotentiality was demonstrated by the stem/progenitors' responses under distinct ex vivo conditions or in vivo when patch grafted as organoids onto the liver versus the pancreas. Therefore, pigs are logical hosts for translational/preclinical studies for cell therapies with these stem/progenitors for hepatic and pancreatic dysfunctions.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"40"},"PeriodicalIF":7.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10158115","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}

{"title":"LRRC10 regulates mammalian cardiomyocyte cell cycle during heart regeneration.","authors":"Rebecca J Salamon,&nbsp;Megan C McKeon,&nbsp;Jiyoung Bae,&nbsp;Xiaoya Zhang,&nbsp;Wyatt G Paltzer,&nbsp;Kayla N Wanless,&nbsp;Alyssa R Schuett,&nbsp;Dakota J Nuttall,&nbsp;Stephen A Nemr,&nbsp;Rupa Sridharan,&nbsp;Youngsook Lee,&nbsp;Timothy J Kamp,&nbsp;Ahmed I Mahmoud","doi":"10.1038/s41536-023-00316-0","DOIUrl":"https://doi.org/10.1038/s41536-023-00316-0","url":null,"abstract":"<p><p>Leucine-rich repeat containing 10 (LRRC10) is a cardiomyocyte-specific protein, but its role in cardiac biology is little understood. Recently Lrrc10 was identified as required for endogenous cardiac regeneration in zebrafish; however, whether LRRC10 plays a role in mammalian heart regeneration remains unclear. In this study, we demonstrate that Lrrc10^-/- knockout mice exhibit a loss of the neonatal mouse regenerative response, marked by reduced cardiomyocyte cytokinesis and increased cardiomyocyte binucleation. Interestingly, LRRC10 deletion disrupts the regenerative transcriptional landscape of the regenerating neonatal mouse heart. Remarkably, cardiac overexpression of LRRC10 restores cardiomyocyte cytokinesis, increases cardiomyocyte mononucleation, and the cardiac regenerative capacity of Lrrc10^-/- mice. Our results are consistent with a model in which LRRC10 is required for cardiomyocyte cytokinesis as well as regulation of the transcriptional landscape during mammalian heart regeneration.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"39"},"PeriodicalIF":7.2,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10002431","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}

{"title":"3D printing titanium grid scaffold facilitates osteogenesis in mandibular segmental defects.","authors":"Yongfeng Li,&nbsp;Huawei Liu,&nbsp;Chao Wang,&nbsp;Rongzeng Yan,&nbsp;Lei Xiang,&nbsp;Xiaodan Mu,&nbsp;Lingling Zheng,&nbsp;Changkui Liu,&nbsp;Min Hu","doi":"10.1038/s41536-023-00308-0","DOIUrl":"https://doi.org/10.1038/s41536-023-00308-0","url":null,"abstract":"<p><p>Bone fusion of defect broken ends is the basis of the functional reconstruction of critical maxillofacial segmental bone defects. However, the currently available treatments do not easily achieve this goal. Therefore, this study aimed to fabricate 3D-printing titanium grid scaffolds, which possess sufficient pores and basic biomechanical strength to facilitate osteogenesis in order to accomplish bone fusion in mandibular segmental bone defects. The clinical trial was approved and supervised by the Medical Ethics Committee of the Chinese PLA General Hospital on March 28th, 2019 (Beijing, China. approval No. S2019-065-01), and registered in the clinical trials registry platform (registration number: ChiCTR2300072209). Titanium grid scaffolds were manufactured using selective laser melting and implanted in 20 beagle dogs with mandibular segmental defects. Half of the animals were treated with autologous bone chips and bone substances incorporated into the scaffolds; no additional filling was used for the rest of the animals. After 18 months of observation, radiological scanning and histological analysis in canine models revealed that the pores of regenerated bone were filled with titanium grid scaffolds and bone broken ends were integrated. Furthermore, three patients were treated with similar titanium grid scaffold implants in mandibular segmental defects; no mechanical complications were observed, and similar bone regeneration was observed in the reconstructed patients' mandibles in the clinic. These results demonstrated that 3D-printing titanium grid scaffolds with sufficient pores and basic biomechanical strength could facilitate bone regeneration in large-segment mandibular bone defects.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"38"},"PeriodicalIF":7.2,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9874965","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}

{"title":"Author Correction: Adult spiny mice (Acomys) exhibit endogenous cardiac recovery in response to myocardial infarction.","authors":"Hsuan Peng,&nbsp;Kazuhiro Shindo,&nbsp;Renée R Donahue,&nbsp;Erhe Gao,&nbsp;Brooke M Ahern,&nbsp;Bryana M Levitan,&nbsp;Himi Tripathi,&nbsp;David Powell,&nbsp;Ahmed Noor,&nbsp;Garrett A Elmore,&nbsp;Jonathan Satin,&nbsp;Ashley W Seifert,&nbsp;Ahmed Abdel-Latif","doi":"10.1038/s41536-023-00314-2","DOIUrl":"https://doi.org/10.1038/s41536-023-00314-2","url":null,"abstract":"","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"37"},"PeriodicalIF":7.2,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10546115","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}

{"title":"MAP4Ks inhibition promotes retinal neuron regeneration from Müller glia in adult mice.","authors":"Houjian Zhang,&nbsp;Yuli Guo,&nbsp;Yaqiong Yang,&nbsp;Yuqian Wang,&nbsp;Youwen Zhang,&nbsp;Jingbin Zhuang,&nbsp;Yuting Zhang,&nbsp;Mei Shen,&nbsp;Jiankai Zhao,&nbsp;Rongrong Zhang,&nbsp;Yan Qiu,&nbsp;Shiying Li,&nbsp;Jiaoyue Hu,&nbsp;Wei Li,&nbsp;Jianfeng Wu,&nbsp;Haiwei Xu,&nbsp;Steven J Fliesler,&nbsp;Yi Liao,&nbsp;Zuguo Liu","doi":"10.1038/s41536-023-00310-6","DOIUrl":"https://doi.org/10.1038/s41536-023-00310-6","url":null,"abstract":"<p><p>Mammalian Müller glia (MG) possess limited regenerative capacities. However, the intrinsic capacity of mammalian MG to transdifferentiate to generate mature neurons without transgenic manipulations remains speculative. Here we show that MAP4K4, MAP4K6 and MAP4K7, which are conserved Misshapen subfamily of ste20 kinases homologs, repress YAP activity in mammalian MG and therefore restrict their ability to be reprogrammed. However, by treating with a small molecule inhibitor of MAP4K4/6/7, mouse MG regain their ability to proliferate and enter into a retinal progenitor cell (RPC)-like state after NMDA-induced retinal damage; such plasticity was lost in YAP knockout MG. Moreover, spontaneous trans-differentiation of MG into retinal neurons expressing both amacrine and retinal ganglion cell (RGC) markers occurs after inhibitor withdrawal. Taken together, these findings suggest that MAP4Ks block the reprogramming capacity of MG in a YAP-dependent manner in adult mammals, which provides a novel avenue for the pharmaceutical induction of retinal regeneration in vivo.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"36"},"PeriodicalIF":7.2,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9872459","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}

{"title":"Regeneration of tracheal neotissue in partially decellularized scaffolds.","authors":"Zheng Hong Tan, Sayali Dharmadhikari, Lumei Liu, Jane Yu, Kimberly M Shontz, Jacob T Stack, Christopher K Breuer, Susan D Reynolds, Tendy Chiang","doi":"10.1038/s41536-023-00312-4","DOIUrl":"10.1038/s41536-023-00312-4","url":null,"abstract":"<p><p>Extensive tracheal injury or disease can be life-threatening but there is currently no standard of care. Regenerative medicine offers a potential solution to long-segment tracheal defects through the creation of scaffolds that support the generation of healthy neotissue. We developed decellularized tracheal grafts (PDTG) by removing the cells of the epithelium and lamina propria while preserving donor cartilage. We previously demonstrated that PDTG support regeneration of host-derived neotissue. Here, we use a combination of microsurgical, immunofluorescent, and transcriptomic approaches to compare PDTG neotissue with the native airway and surgical controls. We report that PDTG neotissue is composed of native tracheal cell types and that the neoepithelium and microvasculature persisted for at least 6 months. Vascular perfusion of PDTG was established within 2 weeks and the graft recruited multipotential airway stem cells that exhibit normal proliferation and differentiation. Hence, PDTG neotissue recapitulates the structure and function of the host trachea and has the potential to regenerate.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"35"},"PeriodicalIF":6.4,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9816860","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}