CD133 progenitor cells from the bone marrow contribute to retinal pigment epithelium repair.
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 1alpha) 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.
Harris
Jeffrey R
JR
Program in Stem Cell Biology, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610, USA.
Fisher
Robert
R
Jorgensen
Marda
M
Kaushal
Shalesh
S
Scott
Edward W
EW
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010455:Peptides / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse