A Therapeutic Strategy for Choroidal Neovascularization Based on Recruitment of Mesenchymal Stem Cells to the Sites of Lesions

Abstract

Choroidal neovascularization (CNV) is a common cause of severe and irreversible visual loss; however, the treatment of CNV has been hindered by its complex and poorly understood pathogenesis. It has been postulated that bone marrow (BM)-derived cells (BMCs) contribute to CNV, but little is known about the role of mesenchymal stem cells (MSCs) in CNV and their therapeutic potential for CNV treatment. We found that BM-derived MSCs transplanted by intravenous injection into laser-induced CNV mouse models were specifically recruited into CNV lesions, where they differentiated into multiple cell types and participated in the development of neovascularization, without stagnation in other organs. By taking advantage of this recruitment potential, engineered MSCs were used to produce the antiangiogenic pigment epithelial-derived factor (PEDF) at the CNV sites, thereby inhibiting the growth of CNVs and stimulating regressive features. Further studies indicated that the effect may be mediated, at least partly, by retinal pigment epithelial (RPE) cells, which function as important regulators for CNV development. These results suggest that MSCs contribute to CNV and could serve as delivery vehicles of antiangiogenic agents for the treatment of a range of CNV-associated diseases.

Revisiting the role of erythropoietin for treatment of ocular disorders

“…107 Various stem cells such as embryonic stem cells, [108][109][110] hematopoietic stem cells, [111][112][113] mesenchymal stem cells (MSCs), [114][115][116] induced pluripotent stem cells, 117,118 and EPC 119,120 have been shown to demonstrate the capability to regenerate into retinal neurons, 108,[110][111][112][113]117 retinal pigmented epithelium, 109,121,122 and improve blood vessels permeability 123 in both in vitro and in vivo studies. It is noteworthy that the transplanted cells will need to survive the harsh microenvironment before cell programming can occur for the replacement of damaged tissue.…”

Stem-Cell Therapy for Retinal Diseases

“…It has been shown that bone-marrow-derived MSCs accumulate around subretinal membranes induced by retinal laser burns. Intravenous injection of mouse bone-marrow MSCs genetically engineered to secrete pigment epithelium derived factor resulted in smaller neovascular complexes (Hou, 2010). …”

Mesenchymal Stem Cell Transplantation for Retinal Degenerations and Dystrophies: Present and Future

“…Some studies showed that nearly 50% of cells in the new vessels were GFP positive, indicating they arise from bone-marrow. Hou et al (2010) used external BMSC and showed their incorporation in new vessels without significant increase in CNV size. What is more important is that they used induced cells to produce Pigmented Epithelium-Derived Factor (PEDF), a strong antiangiogenic factor.…”