April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Long-term Effects of Intravitreal Administration of GMP-grade Human Bone Marrow-derived CD34+ Cells in NOD-SCID Mice with Acute Retinal Ischemia-Reperfusion Injury
Author Affiliations & Notes
  • Susanna S. Park
    Ophthalmology & Vision Science, Univ of California Davis Eye Ctr, Sacramento, California
  • Sergio Caballero, Jr.
    Pharmacology/Therapeutics,
    University of Florida, Gainesville, Florida
  • Bradley Shibata
    Cell Biol & Human Anatomy, Univ of California-Davis, Davis, California
  • Gerhard Bauer
    Institute for Regenerative Cures, Univ of California Davis, Sacramento, California
  • Kristina I. Forward
    Ophthalmology & Vision Science, Univ of California Davis Eye Ctr, Sacramento, California
  • David G. Telander
    Ophthalmology & Vision Science, Univ of California Davis Eye Ctr, Sacramento, California
  • Paul G. FitzGerald
    Cell Biol & Human Anatomy, Univ of California-Davis, Davis, California
  • Maria B. Grant
    Pharmacology and Therapeutics,
    University of Florida, Gainesville, Florida
  • Jan Nolta
    Institute for Regenerative Cures, Univ of California Davis, Sacramento, California
  • Footnotes
    Commercial Relationships  Susanna S. Park, None; Sergio Caballero, Jr., None; Bradley Shibata, None; Gerhard Bauer, None; Kristina I. Forward, None; David G. Telander, None; Paul G. FitzGerald, None; Maria B. Grant, None; Jan Nolta, None
  • Footnotes
    Support  Research to Prevent Blindness Unrestricted Departmental Grant
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2575. doi:
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      Susanna S. Park, Sergio Caballero, Jr., Bradley Shibata, Gerhard Bauer, Kristina I. Forward, David G. Telander, Paul G. FitzGerald, Maria B. Grant, Jan Nolta; Long-term Effects of Intravitreal Administration of GMP-grade Human Bone Marrow-derived CD34+ Cells in NOD-SCID Mice with Acute Retinal Ischemia-Reperfusion Injury. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2575.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To study the long-term effects of intravitreal administration of Good Manufacturing Practice (GMP)-grade human bone marrow-derived CD34+ cells in NOD-SCID mice with acute retinal ischemia-reperfusion injury in order to determine if there are any long-term safety concerns regarding using these cells intravitreally in treating eyes with retinal vasculopathy such as diabetic retinopathy or retinal vascular occlusion.

Methods: : Acute ischemia-reperfusion injury was induced in the right eye of adult NOD-SCID mice (n = 20) by elevating the intraocular pressure transiently for 2 hours to 80 - 90 mm Hg by infusing Hanks balanced saline solution into the anterior chamber under hydrostatic pressure. Seven days later, 10 injured eyes and 5 normal eyes were injected each intravitreally with 5 x 104 CD34+ cells isolated under GMP-conditions from a healthy human donor bone marrow using the Miltenyi CliniMACS system and suspended in 1 µl PBS. The remaining 10 injured eyes were injected intravitreally with 1 µl PBS. Mice were euthanized 1 day, 6 months and 8 months after intravitreal injection. Both eyes were enucleated and examined by immunohistochemical analysis and H & E staining. Among mice followed for 8 months, electroretinography (ERG) was performed on both eyes just prior to euthanization.

Results: : Immunohistochemical staining showed the presence of large numbers of CD34+ cells in the retinal vasculature 1 day after injection, with identifiable cells seen 6 months after injection. ERG at 8 months following intravitreal injection of CD34+ cells showed a signal comparable to uninjected contralateral eye. Histology of the enucleated eyes with retinal ischemia-reperfusion injury injected with CD34+ cells showed a normal retinal morphology with no intraocular tumor or abnormal tissue growth 8 months following intravitreal cell injection.

Conclusions: : Intravitreal administration of GMP-grade human bone marrow-derived CD34+ cells appears to be well tolerated long-term in eyes with acute retinal ischemic injury. Safety was demonstrated.

Keywords: ischemia • retina • vascular occlusion/vascular occlusive disease 
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