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
相关论文
共 50 条
  • [31] Enriched retinal ganglion cells derived from human embryonic stem cells
    Gill, Katherine P.
    Hung, Sandy S. C.
    Sharov, Alexei
    Lo, Camden Y.
    Needham, Karina
    Lidgerwood, Grace E.
    Jackson, Stacey
    Crombie, Duncan E.
    Nayagam, Bryony A.
    Cook, Anthony L.
    Hewitt, Alex W.
    Pebay, Alice
    Wong, Raymond C. B.
    SCIENTIFIC REPORTS, 2016, 6
  • [32] Platelet-Derived Growth Factor Receptor Alpha as a Marker of Mesenchymal Stem Cells in Development and Stem Cell Biology
    Farahani, Ramin M.
    Xaymardan, Munira
    STEM CELLS INTERNATIONAL, 2015, 2015
  • [33] Enriched retinal ganglion cells derived from human embryonic stem cells
    Katherine P. Gill
    Sandy S. C. Hung
    Alexei Sharov
    Camden Y. Lo
    Karina Needham
    Grace E. Lidgerwood
    Stacey Jackson
    Duncan E. Crombie
    Bryony A. Nayagam
    Anthony L. Cook
    Alex W. Hewitt
    Alice Pébay
    Raymond C. B. Wong
    Scientific Reports, 6
  • [34] Evaluation of the effect of platelet-derived growth factor-BB on the biological activity of human mandibular bone marrow-derived mesenchymal stem cells
    Oura, Yurika
    Ishii, Masakazu
    Miyata, Haruka
    Ikeda, Nao
    Sakurai, Tomoaki
    Suehiro, Fumio
    Komabashiri, Naohiro
    Nishimura, Masahiro
    ARCHIVES OF ORAL BIOLOGY, 2025, 174
  • [35] Platelet-derived growth factor induces chemotaxis of neuroepithelial stem cells
    Forsberg-Nilsson, K
    Behar, TN
    Afrakhte, M
    Barker, JL
    McKay, RDG
    JOURNAL OF NEUROSCIENCE RESEARCH, 1998, 53 (05) : 521 - 530
  • [36] Neuropilin-1 regulates platelet-derived growth factor receptor signalling in mesenchymal stem cells
    Ball, Stephen G.
    Bayley, Christopher
    Shuttleworth, C. Adrian
    Kielty, Cay M.
    BIOCHEMICAL JOURNAL, 2010, 427 : 29 - 40
  • [37] Effect of mesenchymal stem cells and platelet-derived growth factor on the healing of radiation induced ulcer in rats
    Jin, Im Geon
    Kim, Jin Ho
    Wu, Hong-Gyun
    Hwang, Soon Jung
    TISSUE ENGINEERING AND REGENERATIVE MEDICINE, 2016, 13 (01) : 78 - 90
  • [38] Effect of mesenchymal stem cells and platelet-derived growth factor on the healing of radiation induced ulcer in rats
    Im Geon Jin
    Jin Ho Kim
    Hong-Gyun Wu
    Soon Jung Hwang
    Tissue Engineering and Regenerative Medicine, 2016, 13 : 78 - 90
  • [39] Platelet-derived growth factor receptor signalling in mesenchymal stem cells is regulated by neuropilin-1
    Ball, S. G.
    Shuttleworth, C. A.
    Kielty, C. M.
    INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 2010, 91 (06) : A28 - A28
  • [40] Mitogenic signaling via platelet-derived growth factor β in metanephric mesenchymal cells
    Wagner, Brent
    Ricono, Jill M.
    Gorin, Yves
    Block, Karen
    Arar, Mazen
    Riley, Dan
    Choudhury, Goutarn Ghosh
    Abboud, Hanna E.
    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (11): : 2903 - 2911