Human Muller Stem Cell (MIO-M1) Transplantation in a Rat Model of Glaucoma: Survival, Differentiation, and Integration

作者：Natalie D. Bull, Gloria Astrid Limb, Keith R G Martin · 发表于：Investigative Ophthalmology & Visual Science · 年份：2008 · DOI：10.1167/iovs.08-1770 · 被引用次数：117 · 研究领域：Retinal Development and Disorders、Glaucoma and retinal disorders、Pluripotent Stem Cells Research

PURPOSE: Stem cell transplantation is a potential treatment strategy for neurodegenerative diseases such as glaucoma. The Müller stem cell line MIO-M1 can be differentiated to produce retinal neurons and glia. The survival, migration, differentiation, and integration of MIO-M1 cells were investigated in a rat model of glaucoma. The effect of modulating the retinal environment with either chondroitinase ABC or erythropoietin was also studied. METHODS: Intraocular pressure was chronically increased unilaterally by using a laser glaucoma model in adult rats. EGFP-transduced MIO-M1 cells were transplanted into the vitreous or subretinal space of glaucomatous or untreated eyes. Oral immune suppressants were administered to reduce xenograft rejection. Survival, migration, differentiation, and integration of grafted cells were assessed by immunohistochemistry. RESULTS: Transplanted cells survived for 2 to 3 weeks in vivo, although microglia/macrophage infiltration and a reduction in graft survival were seen by 4 weeks. Grafted cells displayed a migratory phenotype with an elongated bipolar shape often oriented toward the retina. Transplanted cells expressed markers such as PSA-NCAM, GFAP, and beta-III-tubulin. The host retina was resistant to MIO-M1 migration, but modification of the local environment with erythropoietin or chondroitinase ABC facilitated retinal infiltration by MIO-M1 cells. CONCLUSIONS: The results demonstrate that differentiating MIO-M1 cells within the glaucomato...