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Improving Stem Cell Transplant as a Treatment for Retinal Degeneration

Researchers have made use of human mesenchymal stem cells to effectively delay retinal degeneration in rats. In this study the authors demonstrate that, as in many other cases, the methodology of delivery matters just as much as the details of the cells used:

Retinal and macular degenerative diseases affect millions of people worldwide. Similar to other neurodegenerative diseases, there are no effective treatments that can stop retinal degeneration or restore degenerative retina. Recent advances in stem cell technology led to development of novel cell-based therapies, some are already in phase I/II clinical trials. Studies from our group and others suggest that human bone marrow-derived mesenchymal stem cells (hBM-MSC) may be a promising source for retinal cell-based therapy.

Currently, one of the major challenges in stem cell-based therapy is how to safely deliver effective doses of cells to the target posterior eye tissues (retina, retinal pigment epithelium (RPE) and choroid), due to the unique anatomy and physiology of the eye. The current subretinal injection method involves three port pars plana, vitrectomy and insertion of a needle that penetrates the retina and, in doing so, detaches the photoreceptor cell layer from the RPE forming subretinal 'blebs'. Limited volumes can be injected and therapeutic effect is restricted to areas proximal to point of injection. Moreover, the subretinal surgery raises a significant safety issue, as the retinal architecture across the entire retina in age-related macular degeneration (AMD) and retinitis pigmentosa (RP) patients is fragile and the surgery can induce mechanical damage, reactive gliosis, and loss of function.

We have recently developed a new cell delivery system that enabled the transplantation of hBM-MSCs as a thin layer across the extravascular spaces of the choroid. We used this system in Royal College of Surgeons (RCS) rats, a widely used model of dry AMD and retinal degeneration. The graft covered most of the area of the back of the eye via a single injection with no retinal detachment or choroidal hemorrhages. Cell transplantation delayed photoreceptor degeneration throughout the whole retina and rescued retinal function for up to 5 months in RCS rats. By contrast, when hBM-MSCs were injected intravitreally, they formed a large cell clamp in the vitreous cavity and retinal function was rescued for a shorter duration, up to 12 weeks following transplantation. These findings suggested that the delivery method significantly affects therapeutic potential of transplanted cells, and that graft location, distance from the retina and graft surface area may be critical parameters for achieving effective treatment.

Link: http://dx.doi.org/10.1016/j.scr.2015.08.007

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