CD133 Progenitor Cells from the Bone Marrow Contribute to Retinal Pigment Epithelium Repair

Abstract

Abstract Our goal was to define a clinically significant population of cells by utilizing a single-step selection process to enrich hematopoietic cells capable of regenerating the retinal pigment epithelium (RPE). Utilizing intravitreal injection of bone marrow cells from a mouse with pigment (C57BL6:gfp) into albino recipient mice (C57BL6:Tyr-), we show that hematopoietic progenitor cells (HPCs) enriched for CD133 can regenerate RPE cells and improve retinal function. The chemokine CXCL12 (stromal cell-derived factor 1α) is essential for migration, incorporation, and RPE regeneration by CD133+ HPCs. Once incorporated, CD133+ HPCs become pigmented, adopt an RPE morphology, and express RPE-specific proteins, leading to partial functional recovery by electroretinogram. Human CD133+ HPCs also incorporate in the retina and assume RPE morphology in nonobese diabetic/severe combined immunodeficient mice xenografts. These data show that a clinically accessible CD133+ hematopoietic cell can home to an injured RPE layer, differentiate into cells with significant RPE morphology, and provide therapeutic functional recovery of the visual cycle.