Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States of America.
Institute for Scientific Research and Technology Services (INDICASAT), Panama City, Republic of Panama.
PLoS One. 2020 Oct 13;15(10):e0240469. doi: 10.1371/journal.pone.0240469. eCollection 2020.
Neural stem cells (NSCs), capable of self-renew and differentiate into neural cells, hold promise for use in studies and treatments for neurological diseases. However, current approaches to obtain NSCs from a live brain are risky and invasive, since NSCs reside in the subventricular zone and the in the hippocampus dentate gyrus. Alternatively, mesenchymal stem cells (MSCs) could be a more available cell source due to their abundance in tissues and easier to access. However, MSCs are committed to producing mesenchymal tissue and are not capable of spontaneously differentiating into neural cells. Thus, the process of reprogramming of MSCs into neural cells to use in clinical and scientific settings has significantly impacted the advancement of regenerative medicine. Previously, our laboratory reported trans-differentiation of MSCs to neural cells through the induced pluripotent stem (iPS) cells state, which was produced by overexpression of the embryonic stem cell gene NANOG. In the current study, we demonstrate that treatment with exosomes derived from NSCs makes MSCs capable of expressing neural cell markers bypassing the generation of iPS cells. An epigenetic modifier, decitabine (5-aza-2'-deoxycytidine), enhanced the process. This novel Xeno and transgene-free trans-differentiation technology eliminates the issues associated with iPS cells, such as tumorigenesis. Thus, it may accelerate the development of neurodegenerative therapies and in vitro neurological disorder models for personalized medicine.
神经干细胞（NSCs）具有自我更新和分化为神经细胞的能力，有望用于神经疾病的研究和治疗。然而，目前从活体大脑中获取 NSCs 的方法具有风险和侵入性，因为 NSCs 存在于侧脑室下区和海马齿状回。相比之下，间充质干细胞（MSCs）由于其在组织中的丰富性和更容易获取，可能是更可用的细胞来源。然而，MSCs 被承诺产生间充质组织，并且不能自发地分化为神经细胞。因此，MSCs 重编程为神经细胞用于临床和科学研究的过程显著推动了再生医学的发展。以前，我们的实验室通过过表达胚胎干细胞基因 NANOG 产生的诱导多能干细胞（iPS）状态，报告了 MSCs 向神经细胞的转分化。在本研究中，我们证明了来源于 NSCs 的外泌体处理使 MSCs 能够表达神经细胞标志物，而无需生成 iPS 细胞。一种表观遗传修饰剂地西他滨（5-氮杂-2'-脱氧胞苷）增强了这一过程。这种新型无异种和转基因的转分化技术消除了与 iPS 细胞相关的问题，如致瘤性。因此，它可能加速神经退行性疾病治疗和个性化医学体外神经紊乱模型的发展。
