Kristen M Stearns-Reider, Michael R Hicks, Katherine G Hammond, Joseph C Reynolds, Alok Maity, Yerbol Z Kurmangaliyev, Jesse Chin, Adam Z Stieg, Nicholas A Geisse, Sophia Hohlbauch, Stefan Kaemmer, Lauren R Schmitt, Thanh T Pham, Ken Yamauchi, Bennett G Novitch, Roy Wollman, Kirk C Hansen, April D Pyle, Rachelle H Crosbie
{"title":"肌支架显示层粘连蛋白疤痕对干细胞功能有害,而肌跨度诱导代偿性纤维化。","authors":"Kristen M Stearns-Reider, Michael R Hicks, Katherine G Hammond, Joseph C Reynolds, Alok Maity, Yerbol Z Kurmangaliyev, Jesse Chin, Adam Z Stieg, Nicholas A Geisse, Sophia Hohlbauch, Stefan Kaemmer, Lauren R Schmitt, Thanh T Pham, Ken Yamauchi, Bennett G Novitch, Roy Wollman, Kirk C Hansen, April D Pyle, Rachelle H Crosbie","doi":"10.1038/s41536-023-00287-2","DOIUrl":null,"url":null,"abstract":"<p><p>We developed an on-slide decellularization approach to generate acellular extracellular matrix (ECM) myoscaffolds that can be repopulated with various cell types to interrogate cell-ECM interactions. Using this platform, we investigated whether fibrotic ECM scarring affected human skeletal muscle progenitor cell (SMPC) functions that are essential for myoregeneration. SMPCs exhibited robust adhesion, motility, and differentiation on healthy muscle-derived myoscaffolds. All SPMC interactions with fibrotic myoscaffolds from dystrophic muscle were severely blunted including reduced motility rate and migration. Furthermore, SMPCs were unable to remodel laminin dense fibrotic scars within diseased myoscaffolds. Proteomics and structural analysis revealed that excessive collagen deposition alone is not pathological, and can be compensatory, as revealed by overexpression of sarcospan and its associated ECM receptors in dystrophic muscle. Our in vivo data also supported that ECM remodeling is important for SMPC engraftment and that fibrotic scars may represent one barrier to efficient cell therapy.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"16"},"PeriodicalIF":6.4000,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017766/pdf/","citationCount":"0","resultStr":"{\"title\":\"Myoscaffolds reveal laminin scarring is detrimental for stem cell function while sarcospan induces compensatory fibrosis.\",\"authors\":\"Kristen M Stearns-Reider, Michael R Hicks, Katherine G Hammond, Joseph C Reynolds, Alok Maity, Yerbol Z Kurmangaliyev, Jesse Chin, Adam Z Stieg, Nicholas A Geisse, Sophia Hohlbauch, Stefan Kaemmer, Lauren R Schmitt, Thanh T Pham, Ken Yamauchi, Bennett G Novitch, Roy Wollman, Kirk C Hansen, April D Pyle, Rachelle H Crosbie\",\"doi\":\"10.1038/s41536-023-00287-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>We developed an on-slide decellularization approach to generate acellular extracellular matrix (ECM) myoscaffolds that can be repopulated with various cell types to interrogate cell-ECM interactions. Using this platform, we investigated whether fibrotic ECM scarring affected human skeletal muscle progenitor cell (SMPC) functions that are essential for myoregeneration. SMPCs exhibited robust adhesion, motility, and differentiation on healthy muscle-derived myoscaffolds. All SPMC interactions with fibrotic myoscaffolds from dystrophic muscle were severely blunted including reduced motility rate and migration. Furthermore, SMPCs were unable to remodel laminin dense fibrotic scars within diseased myoscaffolds. Proteomics and structural analysis revealed that excessive collagen deposition alone is not pathological, and can be compensatory, as revealed by overexpression of sarcospan and its associated ECM receptors in dystrophic muscle. Our in vivo data also supported that ECM remodeling is important for SMPC engraftment and that fibrotic scars may represent one barrier to efficient cell therapy.</p>\",\"PeriodicalId\":54236,\"journal\":{\"name\":\"npj Regenerative Medicine\",\"volume\":\"8 1\",\"pages\":\"16\"},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2023-03-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017766/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"npj Regenerative Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41536-023-00287-2\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Regenerative Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41536-023-00287-2","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
Myoscaffolds reveal laminin scarring is detrimental for stem cell function while sarcospan induces compensatory fibrosis.
We developed an on-slide decellularization approach to generate acellular extracellular matrix (ECM) myoscaffolds that can be repopulated with various cell types to interrogate cell-ECM interactions. Using this platform, we investigated whether fibrotic ECM scarring affected human skeletal muscle progenitor cell (SMPC) functions that are essential for myoregeneration. SMPCs exhibited robust adhesion, motility, and differentiation on healthy muscle-derived myoscaffolds. All SPMC interactions with fibrotic myoscaffolds from dystrophic muscle were severely blunted including reduced motility rate and migration. Furthermore, SMPCs were unable to remodel laminin dense fibrotic scars within diseased myoscaffolds. Proteomics and structural analysis revealed that excessive collagen deposition alone is not pathological, and can be compensatory, as revealed by overexpression of sarcospan and its associated ECM receptors in dystrophic muscle. Our in vivo data also supported that ECM remodeling is important for SMPC engraftment and that fibrotic scars may represent one barrier to efficient cell therapy.
期刊介绍:
Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.