Multiple Sclerosis Research Center of New York, New York, New York 10019, USA.
Stem Cells Transl Med. 2012 Jul;1(7):536-47. doi: 10.5966/sctm.2012-0015. Epub 2012 Jun 28.
Bone marrow mesenchymal stem cell-derived neural progenitors (MSC-NPs) are a potential therapeutic source of cells that have been shown to be efficacious in a preclinical model of multiple sclerosis (MS). To examine the feasibility of using MSC-NPs as an autologous source of cells to promote central nervous system (CNS) repair in MS, this study characterized human MSC-NPs from a panel of both MS and non-MS donors. Expanded MSCs showed similar characteristics in terms of growth and cell surface phenotype, regardless of the donor disease status. MSC-NPs derived from all MSCs showed a consistent pattern of gene expression changes that correlated with neural commitment and increased homogeneity. Furthermore, the reduced expression of mesodermal markers and reduced capacity for adipogenic or osteogenic differentiation in MSC-NPs compared with MSCs suggested that MSC-NPs have reduced potential of unwanted mesodermal differentiation upon CNS transplantation. The immunoregulatory function of MSC-NPs was similar to that of MSCs in their ability to suppress T-cell proliferation and to promote expansion of FoxP3-positive T regulatory cells in vitro. In addition, MSC-NPs promoted oligodendroglial differentiation from brain-derived neural stem cells that correlated with the secretion of bioactive factors. Our results provide a set of identity characteristics for autologous MSC-NPs and suggest that the in vitro immunoregulatory and trophic properties of these cells may have therapeutic value in the treatment of MS.
骨髓间充质干细胞源性神经祖细胞 (MSC-NPs) 是一种有潜力的治疗细胞来源,已在多发性硬化症 (MS) 的临床前模型中证明有效。为了研究将 MSC-NPs 用作自身细胞来源以促进 MS 中枢神经系统 (CNS) 修复的可行性,本研究对来自 MS 和非 MS 供体的 MSC-NPs 进行了特征分析。
无论供体疾病状态如何,扩增的 MSC 在生长和细胞表面表型方面均具有相似的特征。所有 MSC 衍生的 MSC-NPs 均表现出一致的基因表达变化模式,与神经定向和增加的均一性相关。此外,与 MSC 相比,MSC-NPs 中中胚层标记物的表达降低,并且向脂肪细胞和成骨细胞分化的能力降低,这表明 MSC-NPs 在 CNS 移植后具有降低的中胚层分化的潜在风险。
MSC-NPs 的免疫调节功能与其抑制 T 细胞增殖和促进 FoxP3 阳性 T 调节细胞体外扩增的能力相似。此外,MSC-NPs 促进了脑源性神经干细胞向少突胶质细胞的分化,这与生物活性因子的分泌有关。
我们的研究结果为自体 MSC-NPs 提供了一组特征,并表明这些细胞的体外免疫调节和营养特性可能在治疗 MS 方面具有治疗价值。