Intravitreal administration of human bone marrow CD34+ stem cells in a murine model of retinal degeneration

Elad Moisseiev, Zeljka McBride, Sharon Oltjen, Pengfei Zhang, Robert Zawadzki, Monica Motta, Christopher J Murphy, Whitney Cary, Geralyn Annett, Jan Nolta, Susanna Soon Chun Park

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Purpose. 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. Methods. 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 electroreti-nography (ERG). Eyes were harvested after euthanasia for immunohistochemical and microarray analysis of the retina. Results. 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. Conclusions. 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.

Original languageEnglish (US)
Article number25
Pages (from-to)4125-4135
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number10
DOIs
StatePublished - Aug 1 2016

Keywords

  • CD34+
  • Intravitreal
  • Retinal degeneration
  • Stem cells

ASJC Scopus subject areas

  • Medicine(all)
  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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