Adult Human Peripheral Blood Mononuclear Cells Are Capable of Producing Neurocyte or Photoreceptor-Like Cells That Survive in Mouse Eyes After Preinduction With Neonatal Retina

Abstract

Abstract Adult human peripheral blood mononuclear cells (hPBMCs) exhibit pluripotency in vitro and so may be a valuable cell source for regenerative therapies. The efficacy of such therapies depends on the survival, differentiation, migration, and integration capacity of hPBMCs in specific tissues. In this study, we examined these capacities of transplanted hPBMCs in mouse retina as well functional improvement after transplant. We isolated hPBMCs and preinduced them for 4 days in media preconditioned with postnatal day 1 rat retina explants. Preinduction increased the proportions of hPBMCs expressing neural stem cell, neural progenitor cell, or photoreceptor markers as revealed by immunofluorescent staining, flow cytometry, and quantitative real-time polymerase chain reaction. Preinduced hPBMCs were transplanted into the subretinal space of retinal degenerative slow (RDS) and retinal degeneration 1 (RD1) mice. At 1, 3, and 6 months after transplantation, treated eyes of RDS mice were collected and cell phenotype was studied by immunofluorescent staining. Preinduced hPBMCs survived in the subretinal space; migrated away from the injection site and into multiple retinal layers; and expressed neural stem cell, neuronal, and photoreceptor markers. Finally, we assessed RD1 retinal function after subretinal transplantation and found significant improvement at 3 months after transplantation. The ease of harvesting, viability in vivo, capacity to express neuronal and photoreceptor proteins, and capacity for functional enhancement suggest that hPBMCs are potential candidates for cell replacement therapy to treat retinal degenerative diseases. Significance This study provides support for the use of peripheral blood mononuclear cells (PBMCs) as a potential source of pluripotent stem cells for treating retinal degeneration. First, this study demonstrated that PBMCs can differentiate into retinal neuron-like cells in vitro and in vivo. Second, some transplanted cells expressed markers for neural progenitors, mature neurons, or photoreceptors at 1, 3, and 6 months after subretinal injection. Finally, this study showed that PBMC transplantation can improve the function of a degenerated retina.