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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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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.
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.
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.
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.
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