Dametti Sara, Faravelli Irene, Ruggieri Margherita, Ramirez Agnese, Nizzardo Monica, Corti Stefania
Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Francesco Sforza 35, 20122, Milan, Italy.
Mol Neurobiol. 2016 May;53(4):2124-31. doi: 10.1007/s12035-015-9181-7. Epub 2015 May 2.
Neuronal loss is a common substrate of many neurological diseases that still lack effective treatments and highly burden lives of affected individuals. The discovery of self-renewing stem cells within the central nervous system (CNS) has opened the doors to the possibility of using the plasticity of CNS as a potential strategy for the development of regenerative therapies after injuries. The role of neural progenitor cells appears to be crucial, but insufficient in reparative processes after damage. In addition, the mechanisms that regulate these events are still largely unknown. Stem cell-based therapeutic approaches have primarily focused on the use of either induced pluripotent stem cells or induced neural stem cells as sources for cell transplantation. More recently, in vivo direct reprogramming of endogenous CNS cells into multipotent neural stem/progenitor cells has been proposed as an alternative strategy that could overcome the limits connected with both the invasiveness of exogenous cell transplantation and the technical issues of in vitro reprogramming (i.e., the time requested and the limited available amount of directly induced neuronal cells). In this review, we aim to highlight the recent studies on in vivo direct reprogramming, focusing on astrocytes conversion to neurons or to neural stem/precursors cells, in the perspective of future therapeutic purposes for neurological disorders.
神经元丢失是许多神经疾病的常见病理基础，这些疾病仍然缺乏有效的治疗方法，给患者的生活带来了沉重负担。中枢神经系统（CNS）中自我更新干细胞的发现，为利用CNS的可塑性作为损伤后再生治疗发展的潜在策略打开了大门。神经祖细胞的作用似乎至关重要，但在损伤后的修复过程中还不够充分。此外，调节这些事件的机制在很大程度上仍然未知。基于干细胞的治疗方法主要集中在使用诱导多能干细胞或诱导神经干细胞作为细胞移植的来源。最近，将内源性CNS细胞在体内直接重编程为多能神经干细胞/祖细胞已被提出作为一种替代策略，该策略可以克服与外源性细胞移植的侵入性以及体外重编程的技术问题（即所需时间和直接诱导神经元细胞的可用量有限）相关的限制。在这篇综述中，我们旨在突出关于体内直接重编程的最新研究，从神经疾病未来治疗目的的角度，重点关注星形胶质细胞向神经元或神经干/前体细胞的转化。
