The rate of retear after surgical repair remains high.Mesenchymal stem cells(MSCs)have been extensively employed in regenerative medicine for several decades.However,safety and ethical concerns constrain their clinica...The rate of retear after surgical repair remains high.Mesenchymal stem cells(MSCs)have been extensively employed in regenerative medicine for several decades.However,safety and ethical concerns constrain their clinical application.Tendon Stem/Progenitor Cells(TSPCs)-derived exosomes have emerged as promising cellfree therapeutic agents.Therefore,urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms.In this study,TSPC-Exos were found to promote the proliferation,migration,and expression of fibrogenesis markers in BMSCs.Furthermore,TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization.In a rat model of rotator cuff repair,TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface,the biomechanical properties of the repaired tendon,and the function of the joint.Mechanistically,TSPC-Exos exhibited high expression of miR-21a-5p,which regulated the expression of PDCD4.The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation,migration,and fibrogenesis in BMSCs.This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies,potentially benefiting patients with rotator cuff tear in the future.展开更多
Tendinopathy is a challenging complication observed in patients with diabetes mellitus.Tendinopathy usually leads to chronic pain,limited joint motion,and even ruptured tendons.Imaging and histological analyses have r...Tendinopathy is a challenging complication observed in patients with diabetes mellitus.Tendinopathy usually leads to chronic pain,limited joint motion,and even ruptured tendons.Imaging and histological analyses have revealed pathological changes in various tendons of patients with diabetes,including disorganized arrangement of collagen fibers,microtears,calcium nodules,and advanced glycation end product(AGE)deposition.Tendon-derived stem/progenitor cells(TSPCs)were found to maintain hemostasis and to participate in the reversal of tendinopathy.We also discovered the aberrant osteochondrogenesis of TSPCs in vitro.However,the relationship between AGEs and TSPCs in diabetic tendinopathy and the underlying mechanism remain unclear.In this review,we summarize the current findings in this field and hypothesize that AGEs could alter the properties of tendons in patients with diabetes by regulating the proliferation and differentiation of TSPCs in vivo.展开更多
Objective To study the gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells.Methods Total RNA extracted from human bone marrow derived mesenchymal stem cells and tendon cells...Objective To study the gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells.Methods Total RNA extracted from human bone marrow derived mesenchymal stem cells and tendon cells underwent reverse transcription,and the products were labeled with α- 32 P dCTP. The cDNA probes of total RNA were hybridized to cDNA microarray with 1176 genes,and then the signals were analyzed by AtlasImage analysis software Version 1.01a.Results Fifteen genes associated with cell proliferation and signal transduction were up-regulated,and one gene that takes part in cell-to-cell adhesion was down-regulated in tendon cells.Conclusion The 15 up-regulated and one down-regulated genes may be beneficial to the orientational differentiation of mesenchymal stem cells into tendon cells.展开更多
There is accumulating evidence of an increased incidence of tendon disorders in people with diabetes mellitus.Diabetic tendinopathy is an important cause of chronic pain,restricted activity,and even tendon rupture in ...There is accumulating evidence of an increased incidence of tendon disorders in people with diabetes mellitus.Diabetic tendinopathy is an important cause of chronic pain,restricted activity,and even tendon rupture in individuals.Tenocytes and tendon stem/progenitor cells(TSPCs)are the dominant cellular components associated with tendon homeostasis,maintenance,remodeling,and repair.Some previous studies have shown alterations in tenocytes and TSPCs in high glucose or diabetic conditions that might cause structural and functional variations in diabetic tendons and even accelerate the development and progression of diabetic tendinopathy.In this review,the biomechanical properties and histopathological changes in diabetic tendons are described.Then,the cellular and molecular alterations in both tenocytes and TSPCs are summarized,and the underlying mechanisms involved are also analyzed.A better understanding of the underlying cellular and molecular pathogenesis of diabetic tendinopathy would provide new insight for the exploration and development of effective therapeutics.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82172511,81972125 and 82172510)Shenzhen“San-Ming”Project of Medicine(No.SZSM202211019).
文摘The rate of retear after surgical repair remains high.Mesenchymal stem cells(MSCs)have been extensively employed in regenerative medicine for several decades.However,safety and ethical concerns constrain their clinical application.Tendon Stem/Progenitor Cells(TSPCs)-derived exosomes have emerged as promising cellfree therapeutic agents.Therefore,urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms.In this study,TSPC-Exos were found to promote the proliferation,migration,and expression of fibrogenesis markers in BMSCs.Furthermore,TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization.In a rat model of rotator cuff repair,TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface,the biomechanical properties of the repaired tendon,and the function of the joint.Mechanistically,TSPC-Exos exhibited high expression of miR-21a-5p,which regulated the expression of PDCD4.The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation,migration,and fibrogenesis in BMSCs.This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies,potentially benefiting patients with rotator cuff tear in the future.
基金National Natural Science Foundation of China,No.81572187 and No.81871812Jiangsu Provincial Medical Talent,The Project of Invigorating Health Care through Science,Technology and Education,No.ZDRCA2016083+2 种基金Natural Science Foundation of Jiangsu Province for Young Scholars,China,No.BK20200398Entrepreneurship and Innovation Program of Jiangsu Province,China,No.1190000054and The Six Projects Sponsoring Talent Summits of Jiangsu Province,China,No.LGY2017099。
文摘Tendinopathy is a challenging complication observed in patients with diabetes mellitus.Tendinopathy usually leads to chronic pain,limited joint motion,and even ruptured tendons.Imaging and histological analyses have revealed pathological changes in various tendons of patients with diabetes,including disorganized arrangement of collagen fibers,microtears,calcium nodules,and advanced glycation end product(AGE)deposition.Tendon-derived stem/progenitor cells(TSPCs)were found to maintain hemostasis and to participate in the reversal of tendinopathy.We also discovered the aberrant osteochondrogenesis of TSPCs in vitro.However,the relationship between AGEs and TSPCs in diabetic tendinopathy and the underlying mechanism remain unclear.In this review,we summarize the current findings in this field and hypothesize that AGEs could alter the properties of tendons in patients with diabetes by regulating the proliferation and differentiation of TSPCs in vivo.
文摘Objective To study the gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells.Methods Total RNA extracted from human bone marrow derived mesenchymal stem cells and tendon cells underwent reverse transcription,and the products were labeled with α- 32 P dCTP. The cDNA probes of total RNA were hybridized to cDNA microarray with 1176 genes,and then the signals were analyzed by AtlasImage analysis software Version 1.01a.Results Fifteen genes associated with cell proliferation and signal transduction were up-regulated,and one gene that takes part in cell-to-cell adhesion was down-regulated in tendon cells.Conclusion The 15 up-regulated and one down-regulated genes may be beneficial to the orientational differentiation of mesenchymal stem cells into tendon cells.
文摘There is accumulating evidence of an increased incidence of tendon disorders in people with diabetes mellitus.Diabetic tendinopathy is an important cause of chronic pain,restricted activity,and even tendon rupture in individuals.Tenocytes and tendon stem/progenitor cells(TSPCs)are the dominant cellular components associated with tendon homeostasis,maintenance,remodeling,and repair.Some previous studies have shown alterations in tenocytes and TSPCs in high glucose or diabetic conditions that might cause structural and functional variations in diabetic tendons and even accelerate the development and progression of diabetic tendinopathy.In this review,the biomechanical properties and histopathological changes in diabetic tendons are described.Then,the cellular and molecular alterations in both tenocytes and TSPCs are summarized,and the underlying mechanisms involved are also analyzed.A better understanding of the underlying cellular and molecular pathogenesis of diabetic tendinopathy would provide new insight for the exploration and development of effective therapeutics.