Epiretinal transplantation of human bone marrow mesenchymal stem cells rescues retinal and vision function in a rat model of retinal degeneration

Abstract

Vision incapacitation and blindness associated with incurable retinal degeneration affect millions of people worldwide. In this study, 0.25×10(6) human bone marrow stem cells (hBM-MSCs) were transplanted epiretinally in the right eye of Royal College Surgeons (RCS) rats at the age of 28 days. Epiretinally transplanted cells were identified as a thin layer of cells along vitreous cavity, in close proximity to the retina or attached to the lens capsule, up to 6 weeks following transplantation. Epiretinal transplantation delayed photoreceptor degeneration and rescued retinal function up to 20 weeks following cell transplantation. Visual functions remained close to normal levels in epiretinal transplantation rats. No inflammation or any other adverse effects were observed in transplanted eyes. Our findings suggest that transplantation of hBM-MSCs as a thin epiretinal layer is effective for treatment of retinal degeneration in RCS rats, and that transplanting the cells in close proximity to the retina enhances hBM-MSC therapeutic effect compared with intravitreal injection.

Therapeutic efficacy of neural stem cells originating from umbilical cord-derived mesenchymal stem cells in diabetic retinopathy

“…We have previously demonstrated that transplanting MSCs in the vitreous can have a therapeutic effect 17 . According to previous studies, NSCs can be identified in the vitreous cavity for at least 6 weeks after intravitreal transplantation 18 . Furthermore, the cell distribution in a relatively thin cell layer could potentially increase the host-graft interaction.…”

The suprachoroidal space as a route of administration to the posterior segment of the eye

“…Some groups chose to use a hypodermic needle to directly inject into the SCS[36, 53, 59–63]. This can be a challenging procedure, since visualization of the scleral-choroidal plane is not possible with this method, and instead tactile cues must be used to indicate when the sclera has been penetrated.…”

“…The concentration of ketorolac detected in the chorioretina was 208 μg/g after intravitreal injection at 30 min and 57 μg/g after suprachoroidal injection at 1 h[37]. Stem cells injected into the SCS using a novel injector were localized to the extravascular choroid [35, 63, 70]. Furthermore, anterior segment tissues, including lens, aqueous humor, and cornea, were largely spared from drug [27, 28, 36, 61, 66].…”

“…Possible diseases of interest that affect the choroid include noninfectious uveitis, dry forms of AMD, choroideremia, uveal melanoma, and central serous chorioretinopathy. The therapeutic effects of corticosteroids[33, 45, 59, 73, 90], small molecules [29, 36, 46, 47, 69, 72], monoclonal antibodies[33, 62], and cells[35, 63] injected into the SCS have been tested in preclinical and clinical trials. Indeed, phase I/II clinical trial results have been promising[73].…”

Progress of stem/progenitor cell-based therapy for retinal degeneration

“…The right eye of 24 cats after optic nerve injury accepted intravitreal injection of cat BM-MSCs, and it was found that MSCs could steadily express brain-derived neurotrophic factor but did not promote neural axon regeneration or differentiate into neuronal cells to mediate neuroprotection after traumatic optic neuropathy [108]. Moreover, following human BM-MSC transplantation, the degenerating retinal cells of RCS rats were also rescued without the requirement of immunosuppression [109]. …”