The human dermis presents an ongoing problem for regenerative medicine. Current medical management uses various acellular dermal matrices on wound sites. The challenge for scientists is to examine, then to question ac...The human dermis presents an ongoing problem for regenerative medicine. Current medical management uses various acellular dermal matrices on wound sites. The challenge for scientists is to examine, then to question accepted conventional wisdom and to present new concepts. In this paper, Autologous Cell Therapy will be described by using cell culture of autologous dermal fibroblasts and their extracellular matrix as a foundation for rebuilding the dermis in conditioned wound beds. This proposal seems to create a conflict with the medical approach to keeping a wound bed “moist”.展开更多
Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers.Recently,extracellular vesicles(EVs),natur...Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers.Recently,extracellular vesicles(EVs),naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins,lipids,and nucleic acids,have drawn wide attention due to their ability to promote wound healing and tissue regeneration.However,current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes.To circumvent these challenges,bioinspired cell-derived nanovesicles(CDNs)that mimic EVs were obtained by shearing mesenchymal stem cells(MSCs)through membranes with different pore sizes.Physical characterisations and highthroughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs.Moreover,these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway,resulting in enhancement of cell proliferation,cell migration,secretion of growth factors and extracellular matrix proteins,which all promoted tissue regeneration.Of note,MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEGfibrin scaffold and animal model,accelerating wound healing in vitro and in vivo.These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.展开更多
This paper sets out to demonstrate that scraping of the flat dorsal surface of human dermis with a scalpel blade and cell plating without centrifugation can lead to the recognition and identification of the individual...This paper sets out to demonstrate that scraping of the flat dorsal surface of human dermis with a scalpel blade and cell plating without centrifugation can lead to the recognition and identification of the individual packing micro pattern of dermal reticular fibroblasts at confluence. The characteristic alignment of papillary and reticular fibroblasts at right angles to each other led to the positive identification of reticular fibroblasts. A non-enzymatic means of sub-culturing (passaging), which yields fully functional, healthy cells with normal, phenotypic morphology is also described. Implications for published subcutaneous wound healing studies are discussed as well as the confluent reticular fibroblast configuration, interpreted as ananatomic site identity code,which may be the address of a specific fibroblast gene pattern expression.展开更多
文摘The human dermis presents an ongoing problem for regenerative medicine. Current medical management uses various acellular dermal matrices on wound sites. The challenge for scientists is to examine, then to question accepted conventional wisdom and to present new concepts. In this paper, Autologous Cell Therapy will be described by using cell culture of autologous dermal fibroblasts and their extracellular matrix as a foundation for rebuilding the dermis in conditioned wound beds. This proposal seems to create a conflict with the medical approach to keeping a wound bed “moist”.
基金the National University of Singapore(Nano Nash Program A-0004336-00-00&A-000850400-00,Singapore)Nanyang Technological University,Singapore(grant number 001487-00001)+4 种基金the Industry Alignment Fund—Pre-Positioning(IAF-PP)grant(A20G1a0046 and R-148-000-307-305/A0004345-00-00)the Singapore Ministry of Education,under its Singapore Ministry of Education Academic Research Fund Tier 1(10051-MOE AcRF Tier 1:Thematic Call 2020)from Bertrand Czarnythe National University of Singapore Nano-NASH Program(NUHSRO/2020/002/Nano Nash/LOA)the National University of Singapore Yong Loo Lin School of Medicine Nanomedicine Translational Research Program(NUHSRO/2021/034/TRP/09/Nanomedicine)the financial supports from Agency for Science,Technology,and Research(A~*STAR,Singapore)Advanced Manufacturing and Engineering Individual Research Grant(AME IRG)(Project ID:A1883c0013,Singapore)。
文摘Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers.Recently,extracellular vesicles(EVs),naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins,lipids,and nucleic acids,have drawn wide attention due to their ability to promote wound healing and tissue regeneration.However,current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes.To circumvent these challenges,bioinspired cell-derived nanovesicles(CDNs)that mimic EVs were obtained by shearing mesenchymal stem cells(MSCs)through membranes with different pore sizes.Physical characterisations and highthroughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs.Moreover,these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway,resulting in enhancement of cell proliferation,cell migration,secretion of growth factors and extracellular matrix proteins,which all promoted tissue regeneration.Of note,MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEGfibrin scaffold and animal model,accelerating wound healing in vitro and in vivo.These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.
文摘This paper sets out to demonstrate that scraping of the flat dorsal surface of human dermis with a scalpel blade and cell plating without centrifugation can lead to the recognition and identification of the individual packing micro pattern of dermal reticular fibroblasts at confluence. The characteristic alignment of papillary and reticular fibroblasts at right angles to each other led to the positive identification of reticular fibroblasts. A non-enzymatic means of sub-culturing (passaging), which yields fully functional, healthy cells with normal, phenotypic morphology is also described. Implications for published subcutaneous wound healing studies are discussed as well as the confluent reticular fibroblast configuration, interpreted as ananatomic site identity code,which may be the address of a specific fibroblast gene pattern expression.
