Subpopulations of bone marrow mesenchymal stem cells exhibit differential effects on delaying retinal degeneration

Abstract

Purpose: Bone marrow mesenchymal stem cells (BMSCs) have been shown therapeutic functions on retinal degeneration (RD). However, BMSCs are heterogenous, a new strategy for BMSCs treatment of RD by choosing appropriate subpopulations was investigated.

Methods: Two subsets of rat BMSCs, termed as rBMSC1 and rBMSC2, were obtained by cloning method. Specific surface markers were analyzed by flow cytometry, proliferating rate and gene expression were carried out by MTT and RNA sequencing analysis. Their differentiation abilities were confirmed by culturing rBMSCs in adipogenic, osteogenic and chondrogenic differentiation media. rBMSC1 and rBMSC2 were transplanted into subretinal space of RCS rats, their therapeutic functions were confirmed by retinal nuclear layer thickness, apoptotic photoreceptors and electroretinogram.

Results: Both subpopulations expressed MSC marker CD29 and CD90 with null hemacyte antigen CD11b and CD45 expression. On the other hand, rBMSC1 showed higher proliferating rate, stronger colony forming capacity, and more adipogenic and chondrogenic potential than rBMSC2, whereas the latter exhibited increased osteogenic ability. RNA sequencing analysis further showed the differential gene levels relative to proliferation, differentiation and immunoregulation in rBMSC1 and rBMSC2. After transplanted into subretinal space of RCS rats, rBMSC1 showed stronger vision rescue function as compared to rBMSC2, in terms of increased b¬-wave amplitude, restored retinal nuclear layer thickness, and decreased apoptotic photoreceptors, whereas the rescue function of rBMSC2 was essentially no better than the control.

Conclusions: This study provides more information about the heterogeneity of BMSCs and a new strategy for BMSCs treatment of RD by choosing appropriate subpopulations.

Keywords: 721 stem cells • 695 retinal degenerations: cell biology • 412 age-related macular degeneration