The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form.This review aims to provide an overview of the scientific evidence on the biology of adipose tissue,the ...The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form.This review aims to provide an overview of the scientific evidence on the biology of adipose tissue,the role of adipose-derived stem cells,and the indications of adipose tissue grafting in peripheral nerve surgery.Adipose tissue is easily accessible through the lower abdomen and inner thighs.Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress,resulting in variable survival of adipocytes within the first 24 hours.Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts.Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization,and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue.In clinical studies,the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results.Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new,more studies are needed to explore safety and long-term effects on peripheral nerve regeneration.The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated,enzyme-free,and used in the same surgical procedure,e.g.adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction.Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival.Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.展开更多
Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability.Herein,we selected induced pluripotent stem cells(iPSCs)derived exosomes to supplement acellular...Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability.Herein,we selected induced pluripotent stem cells(iPSCs)derived exosomes to supplement acellular nerve grafts(ANGs)with the aim of restoring long-distance peripheral nerve defects.Human fibroblasts were reprogrammed into iPSCs through non-integrating transduction of Oct3/4,Sox2,Klf4,and c-Myc.The obtained iPSCs had highly active alkaline phosphatase expression and expressed Oct4,SSEA4,Nanog,Sox2,which also differentiated into all three germ layers in vivo and differentiated into mature peripheral neurons and Schwann cells(SCs)in vitro.After isolation and biological characteristics of iPSCs-derived exosomes,we found that numerous PKH26-labeled exosomes were internalized inside SCs through endocytotic pathway and exhibited a proliferative effect on SCs that were involved in the process of axonal regeneration and remyelination.After that,we prepared ANGs via optimized chemical extracted process to bridge 15 mm long-distance peripheral nerve gaps in rats.Owing to the promotion of iPSCs-derived exosomes,satisfactory regenerative outcomes were achieved including gait behavior analysis,electrophysiological assessment,and morphological analysis of regenerated nerves.Especially,motor function was restored with comparable to those achieved with nerve autografts and there were no significant differences in the fiber diameter and area of reinnervated muscle fibers.Taken together,our combined use of iPSCs-derived exosomes with ANGs demonstrates good promise to restore long-distance peripheral nerve defects,and thus represents a cell-free strategy for future clinical applications.展开更多
文摘The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form.This review aims to provide an overview of the scientific evidence on the biology of adipose tissue,the role of adipose-derived stem cells,and the indications of adipose tissue grafting in peripheral nerve surgery.Adipose tissue is easily accessible through the lower abdomen and inner thighs.Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress,resulting in variable survival of adipocytes within the first 24 hours.Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts.Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization,and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue.In clinical studies,the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results.Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new,more studies are needed to explore safety and long-term effects on peripheral nerve regeneration.The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated,enzyme-free,and used in the same surgical procedure,e.g.adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction.Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival.Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.
基金supported in part by the National Natural Science Foundation of China of China(Contract Grant No.81702133,81802144)the Research Project of Shanghai Municipal Health Commission(Contract Grant No.20194Y0316)Excellent Youth Training Program of Shanghai Jiaotong University Affiliated Sixth People’s Hospital(Contract Grant No.ynyq202102).
文摘Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability.Herein,we selected induced pluripotent stem cells(iPSCs)derived exosomes to supplement acellular nerve grafts(ANGs)with the aim of restoring long-distance peripheral nerve defects.Human fibroblasts were reprogrammed into iPSCs through non-integrating transduction of Oct3/4,Sox2,Klf4,and c-Myc.The obtained iPSCs had highly active alkaline phosphatase expression and expressed Oct4,SSEA4,Nanog,Sox2,which also differentiated into all three germ layers in vivo and differentiated into mature peripheral neurons and Schwann cells(SCs)in vitro.After isolation and biological characteristics of iPSCs-derived exosomes,we found that numerous PKH26-labeled exosomes were internalized inside SCs through endocytotic pathway and exhibited a proliferative effect on SCs that were involved in the process of axonal regeneration and remyelination.After that,we prepared ANGs via optimized chemical extracted process to bridge 15 mm long-distance peripheral nerve gaps in rats.Owing to the promotion of iPSCs-derived exosomes,satisfactory regenerative outcomes were achieved including gait behavior analysis,electrophysiological assessment,and morphological analysis of regenerated nerves.Especially,motor function was restored with comparable to those achieved with nerve autografts and there were no significant differences in the fiber diameter and area of reinnervated muscle fibers.Taken together,our combined use of iPSCs-derived exosomes with ANGs demonstrates good promise to restore long-distance peripheral nerve defects,and thus represents a cell-free strategy for future clinical applications.
