Neurosciences Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
Expert Opin Biol Ther. 2009 Dec;9(12):1487-97. doi: 10.1517/14712590903321439.
Stem-cell-based therapy is a promising new approach to handling neurodegenerative diseases. One of the most promising cellular sources is bone-marrow-derived mesenchymal stem cells (MSCs) also termed multipotent stromal cells. MSCs represent an autologous source and are abundant and non-tumorigenic. Additionally, MSCs possess the useful characteristics of homing and chemokine secretion.
OBJECTIVE/METHODS: Since neurodegenerative diseases have many pathological processes in common, a specific therapeutic agent could potentially ameliorate the symptoms of several distinct neurodegenerative diseases. In this review we demonstrate the wide variety of mechanisms by which MSCs can influence neurodegenerative processes.
RESULTS/CONCLUSIONS: The mechanisms by which transplanted MSCs influence neurodegenerative diseases can be broadly classified as cellular replacement or paracrine secretion, with the latter subdivided into trophic factor secretion or immunomodulation by cytokines. Emerging research suggests that genetic manipulations before transplantation could enhance the therapeutic potential of MSCs. Such manipulation could turn the cells into a 'Trojan horse', to deliver specific proteins, or promote reprogramming of the MSCs into the neural lineage. Clinical trials testing MSC-based therapies for familial amyotrophic lateral sclerosis and multiple sclerosis are in progress.
基于干细胞的疗法是处理神经退行性疾病的一种很有前途的新方法。最有前途的细胞来源之一是骨髓来源的间充质干细胞（MSCs），也称为多能基质细胞。MSCs 代表自体来源，丰富且无致瘤性。此外，MSCs 具有归巢和趋化因子分泌的有用特性。
目的/方法：由于神经退行性疾病有许多共同的病理过程，一种特定的治疗剂可能潜在地改善几种不同神经退行性疾病的症状。在这篇综述中，我们展示了 MSCs 影响神经退行性过程的多种机制。
结果/结论：移植的 MSCs 影响神经退行性疾病的机制可以广义地分为细胞替代或旁分泌分泌，后者又细分为神经营养因子分泌或细胞因子的免疫调节。新的研究表明，移植前的遗传操作可以增强 MSCs 的治疗潜力。这种操作可以将细胞变成“特洛伊木马”，来输送特定的蛋白质，或促进 MSCs 向神经谱系的重编程。正在进行临床试验，以测试基于 MSC 的疗法治疗家族性肌萎缩侧索硬化症和多发性硬化症。
