title: Intravitreal Administration of Human Bone Marrow CD34+ Stem Cells in a Murine Model of Retinal Degeneration.
abstract: Intravitreal murine lineage-negative bone marrow (BM) hematopoietic cells slow down retinal degeneration. Because human BM CD34+ hematopoietic cells are not precisely comparable to murine cells, this study examined the effect of intravitreal human BM CD34+ cells on the degenerating retina using a murine model.
  
  
  
  C3H/HeJrd1/rd1 mice, immunosuppressed systemically with tacrolimus and rapamycin, were injected intravitreally with PBS (n = 16) or CD34+ cells (n = 16) isolated from human BM using a magnetic cell sorter and labeled with enhanced green fluorescent protein (EGFP). After 1 and 4 weeks, the injected eyes were imaged with scanning laser ophthalmoscopy (SLO)/optical coherence tomography (OCT) and tested with electroretinography (ERG). Eyes were harvested after euthanasia for immunohistochemical and microarray analysis of the retina.
  
  
  
  In vivo SLO fundus imaging visualized EGFP-labeled cells within the eyes following intravitreal injection. Simultaneous OCT analysis localized the EGFP-labeled cells on the retinal surface resulting in a saw-toothed appearance. Immunohistochemical analysis of the retina identified EGFP-labeled cells on the retinal surface and adjacent to ganglion cells. Electroretinography testing showed a flat signal both at 1 and 4 weeks following injection in all eyes. Microarray analysis of the retina following cell injection showed altered expression of more than 300 mouse genes, predominantly those regulating photoreceptor function and maintenance and apoptosis.
  
  
  
  Intravitreal human BM CD34+ cells rapidly home to the degenerating retinal surface. Although a functional benefit of this cell therapy was not seen on ERG in this rapidly progressive retinal degeneration model, molecular changes in the retina associated with CD34+ cell therapy suggest potential trophic regenerative effects that warrant further exploration.
authors.affiliation: Department of Ophthalmology & Vision Science University of California Davis Eye Center, Sacramento, California, United States 2Department of Ophthalmology, Tel Aviv Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Moisseiev
authors.affiliation: Vitreoretinal Research Laboratory, University of California Davis Department of Ophthalmology, University of California, Davis, California, United States.
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Smit-McBride
authors.affiliation: Vitreoretinal Research Laboratory, University of California Davis Department of Ophthalmology, University of California, Davis, California, United States.
authors.forename: Sharon
authors.initials: S
authors.lastname: Oltjen
authors.affiliation: University of California Davis Research Investments in the Sciences and Engineering (RISE) Eye-Pod Laboratory, Department of Cell Biology and Human Anatomy, University of California, Davis, California, United States.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology & Vision Science University of California Davis Eye Center, Sacramento, California, United States 4University of California Davis Research Investments in the Sciences and Engineering (RISE) Eye-Pod Laboratory, Department of Cel.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Zawadzki
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, United States.
authors.forename: Monica
authors.initials: M
authors.lastname: Motta
authors.affiliation: Department of Ophthalmology & Vision Science University of California Davis Eye Center, Sacramento, California, United States 5Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, Un.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Murphy
authors.affiliation: Stem Cell Program, Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, United States.
authors.forename: Whitney
authors.initials: W
authors.lastname: Cary
authors.affiliation: Stem Cell Program, Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, United States.
authors.forename: Geralyn
authors.initials: G
authors.lastname: Annett
authors.affiliation: Stem Cell Program, Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, United States.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Nolta
authors.affiliation: Department of Ophthalmology & Vision Science University of California Davis Eye Center, Sacramento, California, United States.
authors.forename: Susanna S
authors.initials: SS
authors.lastname: Park
mesh_terms: D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012160:Retina / Q000473:pathology*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D041623:Tomography, Optical Coherence
chemical_list: D018952:Antigens, CD34