Li P, Tian H, Li Z, Wang L, Gao F, Ou Q, Lian C, Li W, Jin C, Zhang J, Xu J-Y, Wang J, Zhang J, Wang F, Lu L, Xu G-T
Department of Ophthalmology of Shanghai Tenth People's Hospital, and Tongji Eye Institute, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai, 200072, China.
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Curr Mol Med. 2016;16(6):567-81. doi: 10.2174/1566524016666160607090953.
Bone marrow mesenchymal stem cells (BMSCs) have a therapeutic role in retinal degeneration (RD). However, heterogeneity of BMSCs may be associated with differential therapeutic effects in RD. In order to confirm this hypothesis, two subsets of rat BMSCs, termed rBMSC1 and rBMSC2, were obtained, characterized and functionally evaluated in the treatment of RD of Royal College of Surgeons (RCS) rats. Both subpopulations expressed mesenchymal stem cells (MSC) markers CD29 and CD90, but were negative for hemacyte antigen CD11b and CD45 expression. In comparison with rBMSC2, rBMSC1 showed higher rate of proliferation, stronger colony formation, and increased adipogenic potential, whereas rBMSC2 exhibited higher osteogenic potential. Microarray analysis showed differential gene expression patterns between rBMSC1 and rBMSC2, including functions related to proliferation, differentiation, immunoregulation, stem cell maintenance and division, survival and antiapoptosis. After subretinal transplantation in RCS rats, rBMSC1 showed stronger rescue effect than rBMSC2, including increased b-wave amplitude, restored retinal nuclear layer thickness, and decreased number of apoptotic photoreceptors, whereas the rescue function of rBMSC2 was essentially not better than the control. Histological analysis also demonstrated that rBMSC1 possessed a higher survival rate than rBMSC2 in subretinal space. In addition, treatment of basic fibroblast growth factor, an accompanying event in subretinal injection, triggered more robust increase in secretion of growth factors by rBMSC1 as compared to rBMSC2. Taken together, these results have suggested that the different therapeutic functions of BMSC subpopulations are attributed to their distinct survival capabilities and paracrine functions. The underlying mechanisms responsible for the different functions of BMSC subpopulation may lead to a new strategy for the treatment of RD.
骨髓间充质干细胞（BMSCs）在视网膜变性（RD）中具有治疗作用。然而，BMSCs的异质性可能与RD的不同治疗效果相关。为了证实这一假设，我们获取了大鼠BMSCs的两个亚群，称为rBMSC1和rBMSC2，并对其进行了表征，并在皇家外科学院（RCS）大鼠的RD治疗中进行了功能评估。两个亚群均表达间充质干细胞（MSC）标志物CD29和CD90，但血细胞抗原CD11b和CD45表达呈阴性。与rBMSC2相比，rBMSC1显示出更高的增殖率、更强的集落形成能力和增加的成脂潜能，而rBMSC2表现出更高的成骨潜能。微阵列分析显示rBMSC1和rBMSC2之间存在差异基因表达模式，包括与增殖、分化、免疫调节、干细胞维持和分裂、存活和抗凋亡相关的功能。在RCS大鼠视网膜下移植后，rBMSC1显示出比rBMSC2更强的挽救作用，包括增加b波振幅、恢复视网膜核层厚度和减少凋亡光感受器数量，而rBMSC2的挽救功能基本上并不优于对照组。组织学分析还表明，rBMSC1在视网膜下空间的存活率高于rBMSC2。此外，视网膜下注射时伴随的碱性成纤维细胞生长因子处理，与rBMSC2相比，rBMSC1触发了更强的生长因子分泌增加。综上所述，这些结果表明BMSC亚群的不同治疗功能归因于它们不同的存活能力和旁分泌功能。BMSC亚群不同功能的潜在机制可能会导致一种治疗RD的新策略。
