PRECLINICAL STUDIES: TREATMENT OF MULTIPLE SCLEROSIS AND RETINAL DEGENERATIVE DISEASE USING STEM CELLS

Pluripotent stem cells (PSCs) isolated from an embryo or generated by ectopic expression of transcription factors can self-renew indefinitely and differentiate into all cell types found in the body. PSCs have the highest potential for cell therapies, but they face ethical concerns and technical and safety challenges, including teratoma formation. In contrast, mesenchymal stem cells (MSCs) isolated from adult and perinatal sources do not pose ethical and moral dilemmas. While MSCs isolated from adult sources, such as bone marrow, require invasive procedures, their use may also cause graft verse host disease. Therefore, we have focused on MSCs isolated from perinatal sources such as the umbilical cord (UC). These cells have advantages over adult MSCs in that they are highly proliferative, do not display HLA-DR markers, and thus are not likely to be immunogenic. We tested the therapeutic efficacy of UC-derived MSCs and their derivatives in preclinical studies to treat multiple sclerosis (MS) and retinal degenerative disease (RDD). The specific aims were to 1. production of MSCs for preclinical studies; 2. treatment of MS using MSCs and NSCs; and 3. treatment of RDD using MSCs and RPC. Our results showed that MSC-derived neural stem cells (NSCs) countered the inflammatory response, provided neural protection, and induced neurogenesis in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Likewise, MSC-derived retinal progenitor cells (RPCs) survived, integrated, and migrated into various neural layers of the retina in the rd12 mouse model of retinitis pigmentosa (RP). RPCs promoted retinal structure, function, neural protection, and regeneration of the retina resulting in vision improvement. These highly promising findings are likely to facilitate clinical studies for treating MS and RDD.