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Li Wang, Haibin Tian, Peng Li, Zongyi Li, Chunpin Lian, Qingjian Ou, Lixia Lu, Weiye Li, Guotong Xu; Subpopulations of human umbilical cord mesenchymal stem cells exhibit differential rescusing functions on retinal degeneration in RCS rats. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1382.
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© ARVO (1962-2015); The Authors (2016-present)
To provides more information about the heterogeneity of human umbilical cord mesenchymal stem cells (UCMSCs) and a new strategy for UCMSCs treatment of retinal degeneration (RD) by choosing appropriate subpopulations.
Two subsets of human umbilical cord mesenchymal stem cells (UCMSCs), termed as UCMSC1 and UCMSC2, were isolated by single cell cloning, specific surface markers were analyzed by flow cytometry. Proliferating rate and gene expression were carried out by MTT and RNA sequencing analysis. The gene levels of growth factors and cytokines were measured by Real-time PCR. Their differentiation abilities were confirmed by culturing UCMSC in adipogenic, osteogenic and chondrogenic differentiation media. UCMSC1 and UCMSC2 were transplanted into subretinal space of RCS rats, their therapeutic functions were confirmed by analyzing retinal nuclear layer thickness, apoptotic photoreceptors and electroretinogram.
Both the two subpopulations share similar membrane marker phenotypes. However, UCMSC1 showed stronger ability than UCMSC2 regarding proliferating rate, colony forming ability, adipogenic and osteogenic potential, whereas the latter exhibited increased chondrogenic ability. RNA sequencing analysis further showed the differential gene levels relative to proliferation, differentiation and immunoregulation in UCMSC1 and UCMSC2. After transplanted into subretinal space of RCS rats, UCMSC1 had stronger vision rescue function compared to UCMSC2, including increased b¬-wave amplitude, retinal nuclear layer thickness, and decreased apoptotic photoreceptors. Furthermore, When subjected to interleukin-6 treatment in vitro, mimicking the transplanted MSCs under inflammation condition in RD, UCMSC1 expressed much higher levels of growth factors than UCMSC2, such as bFGF, CNTF, EGF, HGF, PEDF, which indicates that the differential therapeutic capacities of UCMSC subpopulations involve distinct paracrine functions.
Two subpopulations with distinct morphology, proliferation, differentiation potentials, marker expression and gene expression were derived from human UCMSCs. In addition, the different subpopulations of human UCMSCs had distinct therapeutic functions on RD.
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