Photoreceptor Therapy: Generation of Neurosphere-Like Cells from Human Mesenchymal Stem Cells Expressing Erythropoietin

The loss of photoreceptors is a major concern implicated in age-macular degeneration (AMD), a type of neurodegenerative
disorder. Failure to prescribe a suitable treatment due to the lack of understanding of the molecular pathogenesis, and
limited capacity to compensate irreparably damaged photoreceptors in the retina have greatly contributed to the
progression of visual dysfunction. Our previous study has shown that Mesenchymal Stem Cells (MSCs) expressing
erythropoietin (EPO) could commit into photoreceptor cell lineage. However, the efficiency of cell differentiation is
limited. The present study aims to explore the capacity of these MSCs to form neurospheres. The cells were transduced
with lentiviral particles encoding for human EPO and green fluorescent protein (GFP) genes, culture-expanded and
sorted before subjected for differentiation induction into neural precursor cells. Our results showed that MSC-EPO
developed into larger neurosphere and expressed relatively higher expression of nestin compared with MSCs alone when
cultured under neural induction medium. These preliminary findings suggested that MSC-EPO have greater neurogenic
potential than MSCs alone. Further study is needed to evaluate the possibilities of neurosphere to delete differentiate
into functional photoreceptor cells. We believe that the success of neurosphere expansion may potentially be useful in
scaling up the manufacturing of photoreceptors in a shorter time and at an efficient cost for retinal cell replacement
therapy.