Functional impairment of mesenchymal stem cells(MSCs),osteoblast progenitor cells,has been proposed to be a pathological mechanism contributing to bone disorders,such as osteoporosis(the most common bone disease)and o...Functional impairment of mesenchymal stem cells(MSCs),osteoblast progenitor cells,has been proposed to be a pathological mechanism contributing to bone disorders,such as osteoporosis(the most common bone disease)and other rare inherited skeletal dysplasias.Pathological bone loss can be caused not only by an enhanced bone resorption activity but also by hampered osteogenic differentiation of MSCs.The majority of the current treatment options counteract bone loss,and therefore bone fragility by blocking bone resorption.These socalled antiresorptive treatments,in spite of being effective at reducing fracture risk,cannot be administered for extended periods due to security concerns.Therefore,there is a real need to develop osteoanabolic therapies to promote bone formation.Human MSCs emerge as a suitable tool to study the etiology of bone disorders at the cellular level as well as to be used for cell therapy purposes for bone diseases.This review will focus on the most relevant findings using human MSCs as an in vitro cell model to unravel pathological bone mechanisms and the application and outcomes of human MSCs in cell therapy clinical trials for bone disease.展开更多
基金Supported by Instituto de Salud Carlos Ⅲ cofounded by ERDF/ESF,"A way to make Europe",No.PI15/00820 and PI18/00202Basque Country government under the ELKARTEK program,No.kk-2018/00031/BCFundación Mutua Madrilena,No.AP165892017
文摘Functional impairment of mesenchymal stem cells(MSCs),osteoblast progenitor cells,has been proposed to be a pathological mechanism contributing to bone disorders,such as osteoporosis(the most common bone disease)and other rare inherited skeletal dysplasias.Pathological bone loss can be caused not only by an enhanced bone resorption activity but also by hampered osteogenic differentiation of MSCs.The majority of the current treatment options counteract bone loss,and therefore bone fragility by blocking bone resorption.These socalled antiresorptive treatments,in spite of being effective at reducing fracture risk,cannot be administered for extended periods due to security concerns.Therefore,there is a real need to develop osteoanabolic therapies to promote bone formation.Human MSCs emerge as a suitable tool to study the etiology of bone disorders at the cellular level as well as to be used for cell therapy purposes for bone diseases.This review will focus on the most relevant findings using human MSCs as an in vitro cell model to unravel pathological bone mechanisms and the application and outcomes of human MSCs in cell therapy clinical trials for bone disease.
