title: Intravitreal autologous bone marrow CD34+ cell therapy for ischemic and degenerative retinal disorders: preliminary phase 1 clinical trial findings.
abstract: OBJECTIVE
  Because human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions.
  
  
  METHODS
  This prospective study enrolled six subjects (six eyes) with irreversible vision loss from retinal vascular occlusion, hereditary or nonexudative age-related macular degeneration, or retinitis pigmentosa. CD34+ cells were isolated under Good Manufacturing Practice conditions from the mononuclear cellular fraction of the BM aspirate using a CliniMACs magnetic cell sorter. After intravitreal CD34+ cell injection, serial ophthalmic examinations, microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics OCT were performed during the 6-month follow-up.
  
  
  RESULTS
  A mean of 3.4 million (range, 1-7 million) CD34+ cells were isolated and injected per eye. The therapy was well tolerated with no intraocular inflammation or hyperproliferation. Best-corrected visual acuity and full-field ERG showed no worsening after 6 months. Clinical examination also showed no worsening during follow-up except among age-related macular degeneration subjects in whom mild progression of geographic atrophy was noted in both the study eye and contralateral eye at 6-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in vivo imaging using adaptive optics OCT showed changes suggestive of new cellular incorporation into the macula of the hereditary macular degeneration study eye.
  
  
  CONCLUSIONS
  Intravitreal autologous BM CD34+ cell therapy appears feasible and well tolerated in eyes with ischemic or degenerative retinal conditions and merits further exploration. (ClinicalTrials.gov number, NCT01736059.).
authors.affiliation: Department of Ophthalmology and Vision Science, University of California-Davis Eye Center, Sacramento, California, United States.
authors.forename: Susanna S
authors.initials: SS
authors.lastname: Park
authors.affiliation: Institute for Regenerative Cures, University of California-Davis School of Medicine, Sacramento, California, United States.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bauer
authors.affiliation: Division of Hematology and Oncology, University of California-Davis Cancer Center, Sacramento, California, United States.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Abedi
authors.affiliation: Institute for Regenerative Cures, University of California-Davis School of Medicine, Sacramento, California, United States.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Pontow
authors.affiliation: Department of Ophthalmology and Vision Science, University of California-Davis Eye Center, Sacramento, California, United States.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Panorgias
authors.affiliation: Department of Ophthalmology and Vision Science, University of California-Davis Eye Center, Sacramento, California, United States.
authors.forename: Ravi
authors.initials: R
authors.lastname: Jonnal
authors.affiliation: Department of Ophthalmology and Vision Science, University of California-Davis Eye Center, Sacramento, California, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Zawadzki
authors.affiliation: Department of Ophthalmology and Vision Science, University of California-Davis Eye Center, Sacramento, California, United States.
authors.forename: John S
authors.initials: JS
authors.lastname: Werner
authors.affiliation: Institute for Regenerative Cures, University of California-Davis School of Medicine, Sacramento, California, United States.
authors.forename: Jan
authors.initials: J
authors.lastname: Nolta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D017690:Cell Transplantation / Q000379:methods*; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006801:Humans; D058449:Intravitreal Injections; D007511:Ischemia / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D008297:Male; D011446:Prospective Studies; D012162:Retinal Degeneration / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D012164:Retinal Diseases / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D016896:Treatment Outcome; D014792:Visual Acuity; D055815:Young Adult
chemical_list: D018952:Antigens, CD34
keywords: OCT; retinal degeneration; retinal imaging; retinal vein occlusion; stem cells