A therapeutic strategy for choroidal neovascularization based on recruitment of mesenchymal stem cells to the sites of lesions.
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.
Hou
Hui-Yuan
HY
Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Liang
Hong-Liang
HL
Wang
Yu-Sheng
YS
Zhang
Zhao-Xia
ZX
Wang
Bai-Ren
BR
Shi
Yuan-Yuan
YY
Dong
Xiao
X
Cai
Yan
Y
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
D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor