Optic neuropathies, including glaucoma, are characterized by progressive degeneration of retinal ganglion cells (RGCs). This characteristic process makes this group of diseases suitable candidates for cellular therapy.
1 Stem cell-based treatment had become a promising frontier for treating neurodegenerative diseases, thus making it a potential therapeutic approach for optic neuropathies as well.
1 –8 There are several candidate cells for use in stem cell therapy to the retina, including embryonal stem cells, oligodendrocyte precursor cells, human Müller stem cells, and bone marrow–derived stem cells.
9 –13 Bone marrow–derived mesenchymal stem cells (MSCs) are self-renewing precursors that reside in the bone marrow. They are best characterized by their capacity to differentiate into connective tissue cell types but have also been reported to exhibit the ability to differentiate in vitro and in vivo into nonmesodermal cell types, such as neural-like cells.
14 –17 Numerous studies have evaluated the efficacy of MSCs to promote repair and regeneration of nervous tissue within the central and peripheral nervous systems, although the exact mechanisms responsible for a beneficial outcome remain indeterminate.
18 –24 Possible effects include cell replacement, trophic factor delivery, and immunomodulation.
25 Previous reports have suggested that the adult retina does not provide a permissive environment in which transplanted stem cells can easily migrate and integrate.
3,26,27 In addition, replacement of lost RGCs will require the construction of complex axonal connections within the retina and to the brain. As such, the trophic factor delivery characteristic of MSCs may present a more practical approach and may be beneficial as supportive therapy for dying RGCs. According to this approach, MSC effectiveness may be credited to the production of neurotrophic factors that support neuronal cell survival, induce endogenous cell proliferation, and promote nerve fiber regeneration at sites of injury. Indeed, mounting evidence suggests that supplemental therapy with neurotrophic factors either by intravitreal injections or by gene therapy is neuroprotective in models of optic nerve injuries, including optic nerve transection (ONT) and glaucoma.
28 –34 To take this approach one step forward, we used a novel approach that we designed for inducing the differentiation of human and rat MSCs toward NTF-SCs to deliver neurotrophic factors by transplantation of stem cells.