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
  • [21] Biological effects of melatonin on human adipose-derived mesenchymal stem cells
    Heo, June Seok
    Pyo, Sangshin
    Lim, Ja-Yun
    Yoon, Dae Wui
    Kim, Bo Yong
    Kim, Jin-Hee
    Kim, Gi Jin
    Lee, Seung Gwan
    Kim, Jinkwan
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2019, 44 (06) : 2234 - 2244
  • [22] Pigment Epithelium-Derived Factor Released by Muller Glial Cells Exerts Neuroprotective Effects on Retinal Ganglion Cells
    Unterlauft, Jan Darius
    Eichler, Wolfram
    Kuhne, Konstantin
    Yang, Xiu Mei
    Yafai, Yousef
    Wiedemann, Peter
    Reichenbach, Andreas
    Claudepierre, Thomas
    NEUROCHEMICAL RESEARCH, 2012, 37 (07) : 1524 - 1533
  • [23] Paracrine-Mediated Neuroprotection and Neuritogenesis of Axotomised Retinal Ganglion Cells by Human Dental Pulp Stem Cells: Comparison with Human Bone Marrow and Adipose-Derived Mesenchymal Stem Cells
    Mead, Ben
    Logan, Ann
    Berry, Martin
    Leadbeater, Wendy
    Scheven, Ben A.
    PLOS ONE, 2014, 9 (10):
  • [24] Mesenchymal stem cells attenuate hydrogen peroxide-induced oxidative stress and enhance neuroprotective effects in retinal ganglion cells
    Cui, Yi
    Xu, Nuo
    Xu, Wei
    Xu, Guoxing
    IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, 2017, 53 (04) : 328 - 335
  • [25] Quantitative Retinal Protein Analysis after Optic Nerve Transection Reveals a Neuroprotective Role for Hepatoma-Derived Growth Factor on Injured Retinal Ganglion Cells
    Hollander, Adam
    D'Onofrio, Philippe M.
    Magharious, Mark M.
    Lysko, Meghan D.
    Koeberle, Paulo D.
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2012, 53 (07) : 3973 - 3989
  • [26] Hepatocyte growth factor promotes the proliferation of human embryonic stem cell derived retinal pigment epithelial cells
    Karamali, Fereshteh
    Esfahani, Mohammad-Hossein Nasr
    Hajian, Mehdi
    Ejeian, Fatemeh
    Satarian, Leila
    Baharvand, Hossein
    JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (04) : 4256 - 4266
  • [27] TNFα-Mediated Priming of Mesenchymal Stem Cells Enhances Their Neuroprotective Effect on Retinal Ganglion Cells
    Mead, Ben
    Chamling, Xitiz
    Zack, Donald J.
    Ahmed, Zubair
    Tomarev, Stanislav
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2020, 61 (02)
  • [28] Individual Variation in Growth Factor Concentrations in Platelet-rich Plasma and Its Influence on Human Mesenchymal Stem Cells
    Cho, Hee Soon
    Song, In Hwan
    Park, So-Young
    Sung, Min Cheol
    Ahn, Myun-Whan
    Song, Kyung Eun
    KOREAN JOURNAL OF LABORATORY MEDICINE, 2011, 31 (03): : 212 - 218
  • [29] Quantitation of platelet-derived growth factor receptors in human arterial smooth muscle cells in vitro
    Krettek, A
    Fager, G
    Jernberg, P
    OstergrenLunden, G
    Lustig, F
    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1997, 17 (11) : 2395 - 2404
  • [30] Fibroblast Growth Factor 2 and Platelet-Derived Growth Factor, but Not Platelet Lysate, Induce Proliferation-Dependent, Functional Class II Major Histocompatibility Complex Antigen in Human Mesenchymal Stem Cells
    Bocelli-Tyndall, Chiara
    Zajac, Paul
    Di Maggio, Nunzia
    Trella, Emanuele
    Benvenuto, Federica
    Iezzi, Giandomenica
    Scherberich, Arnaud
    Barbero, Andrea
    Schaeren, Stefan
    Pistoia, Vito
    Spagnoli, Giulio
    Vukcevic, Mirko
    Martin, Ivan
    Tyndall, Alan
    ARTHRITIS AND RHEUMATISM, 2010, 62 (12): : 3815 - 3825