title: 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.
authors.affiliation: Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Hou
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Liang
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Wang
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Bai-Ren
authors.initials: BR
authors.lastname: Wang
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Shi
authors.forename: Xiao
authors.initials: X
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor