Neuroprotective Effects of Human Mesenchymal Stem Cells and Platelet-Derived Growth Factor on Human Retinal Ganglion Cells

被引:58
|
作者
Osborne, Andrew [1 ]
Sanderson, Julie [2 ]
Martin, Keith R. [1 ,3 ,4 ,5 ]
机构
[1] Univ Cambridge, John van Geest Ctr Brain Repair, Cambridge CB2 0PY, England
[2] Univ East Anglia, Sch Pharm, Norwich, Norfolk, England
[3] Cambridge NIHR Biomed Res Ctr, Cambridge, England
[4] Addenbrookes Hosp, Eye Dept, Cambridge, England
[5] Wellcome Trust Med Res Council, Stem Cell Inst, Cambridge, England
基金
英国惠康基金;
关键词
Mesenchymal stem cells; Neuroprotection; Human; Retina; Degeneration; CILIARY NEUROTROPHIC FACTOR; OCULAR HYPERTENSION; INFLAMMATORY STIMULATION; EXPERIMENTAL GLAUCOMA; DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; AXON REGENERATION; IN-VITRO; PDGF; SURVIVAL;
D O I
10.1002/stem.2722
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Optic neuropathies such as glaucoma occur when retinal ganglion cells (RGCs) in the eye are injured. Strong evidence suggests mesenchymal stem cells (MSCs) could be a potential therapy to protect RGCs; however, little is known regarding their effect on the human retina. We, therefore, investigated if human MSCs (hMSCs), or platelet-derived growth factor (PDGF) as produced by hMSC, could delay RGC death in a human retinal explant model of optic nerve injury. Our results showed hMSCs and the secreted growth factor PDGF-AB could substantially reduce human RGC loss and apoptosis following axotomy. The neuroprotective pathways AKT, ERK, and STAT3 were activated in the retina shortly after treatments with labeling seen in the RGC layer. A dose dependent protective effect of PDGF-AB was observed in human retinal explants but protection was not as substantial as that achieved by culturing hMSCs on the retina surface which resulted in RGC cell counts similar to those immediately post dissection. These results demonstrate that hMSCs and PDGF have strong neuroprotective action on human RGCs and may offer a translatable, therapeutic strategy to reduce degenerative visual loss.
引用
收藏
页码:65 / 78
页数:14
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