Human adult bone marrow-derived somatic cells rescue vision in a rodent model of retinal degeneration

Visual impairment associated with photoreceptor degeneration is a largely untreatable condition affecting millions of people worldwide. Cellular therapies offer an attractive alternative for the treatment of retinal degeneration. Human adult bone marrow-derived somatic cells (hABM-SCs) present particular advantages for interventional therapy to the eye because they are non-immunogenic, effective at low dose, maintain a stable phenotype and secrete factors known to promote photoreceptor cell survival. Here we assess the potential of hABM-SCs (developed by Garnet BioTherapeutics) to sustain vision in a rodent model of human retinal disease-the Royal College of Surgeons (RCS) rat. A cell suspension of 5 × 10 4 cells in 2 μl carrying medium was injected into the subretinal space of RCS rats at P21, control animals received medium alone and untreated. Animals were maintained with/without oral cyclosporine A through the experimental period. Visual functions including optokinetic response (OKR) and luminance threshold recording were conducted in both cell-treated and control animals. Histological study was performed afterward to examine donor cell survival and photoreceptor rescue. OKR measured at P60 and P90 in cell-injected groups with/without immunosuppression was significantly better than controls ( P < 0.01). Luminance threshold recordings around P90-100 also showed much lower threshold in cell-injected eyes with best result of 0.8 log units above background (compared with 0.4 log units in wild type retina), while sham-injected and untreated eyes gave values of 2.7 and 3.5 log units respectively. Histological examination revealed that there were 3–6 layers of photoreceptors in cell-injected eyes at P100; but only one layer in sham-injected and untreated controls. There was no evidence of unwanted pathology. This study has demonstrated that a human cell product that can be manufactured under conditions acceptable for clinical use and in quantities sufficient for treating large numbers of patients can rescue photoreceptors and sustain substantial visual function when injected into the subretinal space of a rodent model for retinal degeneration. Furthermore, we have shown that achieving a therapeutic benefit does not require the cells to persist and does not require immunosuppression.