摘要
骨髓间充质干细胞(BMSCs)在视网膜变性(RD)中有治疗作用。然而,异质性骨髓间充质干细胞可能与视网膜变性的秩序差疗效相关的。为了证实这一假设,两大鼠骨髓间充质干细胞亚群,被称为rBMSC 1和rBMSC 2,在视网膜变性处理的爱尔兰皇家外科学院治疗(RCS)大鼠得到特征和功能评价。这两个亚群表达间充质干细胞(MSC)标记CD29和CD90,但均为阴性,血细胞抗原CD11b和CD45表达。比较rBMSC 2,rBMSC 1显示增殖率高、较强的集落形成,增加脂肪细胞的潜力,而rbmsc2具有较高的成骨潜能。微阵列分析显示基因差异表达模式rBMSC 1和rBMSC 2之间,包括增殖、分化、免疫调节相关的功能,干细胞的维持和分工,生存和抗凋亡。爱尔兰皇家外科学院治疗大鼠视网膜下移植后,rBMSC 1比rBMSC 2更强的救援效果,包括增加的b波振幅,恢复视网膜核层厚度及凋亡细胞数下降,而rBMSC 2救援功能基本上是不是比控制。组织学分析表明,视网膜下间隙中rBMSC 1具有较高的存活率比rBMSC 2。此外,碱性成纤维细胞生长因子治疗,视网膜下注射伴随的事件,引发了更强大的生长因子的分泌增加rBMSC 1相比rBMSC 2。总之,这些结果表明,骨髓间充质干细胞亚群不同的治疗作用是由于其独特的生存能力和分泌功能。机制负责骨髓间充质干细胞亚群功能的不同可能会导致视网膜变性的治疗新策略
关键词: 骨髓间充质干细胞亚群,治疗功能,分泌功能,视网膜变性。
Current Molecular Medicine
Title:Subpopulations of Bone Marrow Mesenchymal Stem Cells Exhibit Differential Effects in Delaying Retinal Degeneration
Volume: 16 Issue: 6
Author(s): P. Li, H. Tian, Z. Li, L. Wang, F. Gao, Q. Ou, C. Lian, W. Li, C. Jin, J. Zhang, J.-Y. Xu, J. Wang, J. Zhang, F. Wang, L. Lu and G.-T. Xu
Affiliation:
关键词: 骨髓间充质干细胞亚群,治疗功能,分泌功能,视网膜变性。
摘要: 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.
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P. Li, H. Tian, Z. Li, L. Wang, F. Gao, Q. Ou, C. Lian, W. Li, C. Jin, J. Zhang, J.-Y. Xu, J. Wang, J. Zhang, F. Wang, L. Lu and G.-T. Xu , Subpopulations of Bone Marrow Mesenchymal Stem Cells Exhibit Differential Effects in Delaying Retinal Degeneration, Current Molecular Medicine 2016; 16 (6) . https://dx.doi.org/10.2174/1566524016666160607090953
DOI https://dx.doi.org/10.2174/1566524016666160607090953 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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