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Shaomei Wang, YuChun Tsai, Sergey Girman, Lin Shen, Catherine Morgans, Grazyna Adamus, Weidong Xiong, Vaithi Arumugaswami, Clive Svendsen, Bin Lu; Manipulating MSC Homing To Enhance Its Efficacy in Preserving Vision. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4201. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The advance in stem cell biology has shown great promise to treat neurodegenerative diseases. Among the renewable cell sources, bone marrow derived mesenchymal stem cells (MSC) have been used widely both in clinics and research. The major advantage of using MSC is that they can be delivered intravenously, which offers extensive protection compared with local injection and can be redosed without side effect. Here we investigate whether manipulating MSC homing would enhance its efficacy in preserving vision.
Methods: MSC were isolated from the Royal College Surgeon (RCS) rats as described before. RCS rats at postnatal day (p) 21-23 and P60 received intravenous injection of MSC. The following groups were studied: 1) MSC without pretreatment; 2) MSC were cultured in the hypoxia; 3) subretinal injection of cells/medium into the RCS rats, 3 days later, intravenous injection of MSC; 4) subretinal injection of cells/medium into the RCS rats, 3 days later, intravenous injection of MSC that were incubated with CXCR4 antibody. The efficacy of above treatments were examined by optokinetic response, electroretinogram and luminance threshold recording from the superior colliculus; and retinal histology.
Results: Intravenous injection of MSC without any treatment can preserve photoreceptors and visual function; limit the development of vascular pathology associated with retinal degeneration. Increased expression of CXCR4 on the MSC or increased expression of SDF-1a in the retina tremendously enhanced efficacy of MSC homing and preservation of visual function.
Conclusions: Intravenous delivery of MSC offers preservation of vision at early and later stages of degeneration. Manipulating the expression of SDF-1/CXCR4 can enhance the efficacy of MSC in preserving vision.
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