Alzheimer’s disease (AD) is the common cause of dementia which shows the neuro-pathologies like an accumulation of amyloid-</span><i style="font-family:""><span style="font-family:V...Alzheimer’s disease (AD) is the common cause of dementia which shows the neuro-pathologies like an accumulation of amyloid-</span><i style="font-family:""><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;"> (A</span><i style="font-family:""><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">) and degeneration of cholinergic neuron. Olfactory bulbectomized (OBX) mice show some of AD features, so they have been used to research as AD model. Mesenchymal stem cells (MSCs) can differentiate into many kinds of cells, including neuronal cells. In this study, we intranasally administrated the conditioned medium derived from cultured umbilical cord (UC) MSCs. The intranasal administration of the MSCs medium restored the cognitive impairment observed in OBX mice. In addition, the decreased number of choline acetyltransferase-positive cells in the medial septum was restored by the conditioned medium administration. In conclusion, MSCs-derived conditioned medium may have protective effects of cholinergic neurons in the medial septum, thereby rescuing the cognitive impairment of OBX.展开更多
The process of bone repair is highly regulated by a large number of bioactive factors.Thus,a“cocktail”of bioactive factors supplemented to the defect sites is desirable for bone repair.In this regard,small extracell...The process of bone repair is highly regulated by a large number of bioactive factors.Thus,a“cocktail”of bioactive factors supplemented to the defect sites is desirable for bone repair.In this regard,small extracellular vesicles(sEVs)derived from mesenchymal stem cells hold great potential in tissue repair.Nevertheless,the poor homing and retention of sEVs greatly limited their possible clinical application.In the present work,DMPE-PEG-CREKA was inserted into the membrane of sEVs released from adipose-derived mesenchymal stem cells to obtain CREKA functionalized sEVs(CREKA-sEVs),which could target fibrin to accumulate and retain in bone defects.Our results showed that CREKA-sEVs,like sEVs,promoted the osteogenic differentiation of BMSCs,the angiogenic property of HUVECs,and modulated the polarization of macrophages in vitro.Furthermore,due to the improved fibrin-binding and retention capacity of CREKA-sEVs,they enhanced the bone repair substantially in the rat femoral defect model.This study provided a new strategy to improve the therapeutic efficiency of sEVs and showed that CREKA-sEVs had great application value in bone tissue repair.展开更多
文摘Alzheimer’s disease (AD) is the common cause of dementia which shows the neuro-pathologies like an accumulation of amyloid-</span><i style="font-family:""><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;"> (A</span><i style="font-family:""><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">) and degeneration of cholinergic neuron. Olfactory bulbectomized (OBX) mice show some of AD features, so they have been used to research as AD model. Mesenchymal stem cells (MSCs) can differentiate into many kinds of cells, including neuronal cells. In this study, we intranasally administrated the conditioned medium derived from cultured umbilical cord (UC) MSCs. The intranasal administration of the MSCs medium restored the cognitive impairment observed in OBX mice. In addition, the decreased number of choline acetyltransferase-positive cells in the medial septum was restored by the conditioned medium administration. In conclusion, MSCs-derived conditioned medium may have protective effects of cholinergic neurons in the medial septum, thereby rescuing the cognitive impairment of OBX.
基金supported by the National Key R&D Program of China(2021YFB3800900)National Natural Science Foundation of China(31971266,51232002)+1 种基金the Key Research and Development Program of Guangzhou(202007020002)Guangdong Province Basic and Applied Research Foundation(2022A1515011925).
文摘The process of bone repair is highly regulated by a large number of bioactive factors.Thus,a“cocktail”of bioactive factors supplemented to the defect sites is desirable for bone repair.In this regard,small extracellular vesicles(sEVs)derived from mesenchymal stem cells hold great potential in tissue repair.Nevertheless,the poor homing and retention of sEVs greatly limited their possible clinical application.In the present work,DMPE-PEG-CREKA was inserted into the membrane of sEVs released from adipose-derived mesenchymal stem cells to obtain CREKA functionalized sEVs(CREKA-sEVs),which could target fibrin to accumulate and retain in bone defects.Our results showed that CREKA-sEVs,like sEVs,promoted the osteogenic differentiation of BMSCs,the angiogenic property of HUVECs,and modulated the polarization of macrophages in vitro.Furthermore,due to the improved fibrin-binding and retention capacity of CREKA-sEVs,they enhanced the bone repair substantially in the rat femoral defect model.This study provided a new strategy to improve the therapeutic efficiency of sEVs and showed that CREKA-sEVs had great application value in bone tissue repair.
