Long-Term Effects of Intravitreal Injection of GMP-Grade Bone-Marrow–Derived CD34⁺Cells in NOD-SCID Mice with Acute Ischemia-Reperfusion Injury

Abstract

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. A clinical trial will start to further explore this therapy.

Circulating Mononuclear Progenitor Cells: Differential Roles for Subpopulations in Repair of Retinal Vascular Injury

“…34 Therefore, the use of bone marrow stem cells, specifically human CD34 þ cells, is an exciting potential therapy for the treatment of retinal vascular disease in humans. Ideally, patients would be treated with their own cells, and this would eliminate any complications resulting from rejection of donor stem/progenitor cells.…”

Prospects of Stem Cells for Retinal Diseases

“…22Y26,29,32Y37 Moreover, preclinical Good Manufacturing PracticeYcompliant studies can ensure that stem cells and the derived cells are safe and would not form teratoma in the immunedeficient mice. 25,29 In addition, there are ongoing clinical trials of ESC-derived retinal pigment epithelial cells, bone marrowY derived mononuclear cells, and umbilical tissueYderived cells on different retinal diseases. 45,47 They are the stepping stone toward the application of stem cell products in human subjects.…”

“…Endothelial progenitor cells, which have the ability to home in on areas of vascular insufficiency and to participate in endothelial repair and neovascularization, have been proposed to be used in the clinical trial for diabetic retinopathy. 28,29 Although adult stem cells, such as MSC, are able to be induced into retinal cells in vitro, 30,31 they showed no evidence of differentiation into retinal cells or integration into retina after intravitreal grafting into the animal eyes. 32 Nevertheless, intravitreal transplantation of MSC promotes photoreceptor cell survival in an animal model for retinitis pigmentosa 33,34 and increase retinal ganglion cell survival and reduce retinal ganglion cell axon loss in an animal model for glaucoma.…”

“…25,29 Long-term data (spanning the life of the animals) is needed to provide the evidence of no teratoma formation. However, because stem cell products become more widespread and regulated under various conditions, there is an increasing need for global standardization and regulation of the processes to ensure viable application of these products in a clinical setting.…”

Stem cells in retinal regeneration: past, present and future

“…The same group is currently recruiting to use this therapy on subjects with AMD and vascular retinopathies such as retinal vein occlusion and diabetic retinopathy, both of which result in retinal ischaemia. In California, another group is recruiting for a trial that uses intravitreal injection of autologous BMHSCs to treat retinal vein occlusion, following their use in animal studies in which they were deemed to be safe (Park et al, 2012).…”