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Editors Selection IGR 22-2

Basic Science: Neuroprotection

Comment by Derek Welsbie on:

74614 Neuroprotective Effects of Human Mesenchymal Stem Cells and Platelet-Derived Growth Factor on Human Retinal Ganglion Cells, Osborne A; Sanderson J; Martin KR, Stem Cells, 2018; 36: 65-78

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Mesenchymal stem cells (MSCs) are the stem cells found in bone marrow and are responsible for producing cartilage, adipose and bone tissue. While these stem cells lack the capacity to regenerate retinal ganglion cells (RGCs), multiple groups have demonstrated that intravitreal injection of MSCs can prevent RGC loss in rodent models of optic neuropathy. Keith Martin's group at University of Cambridge has previously shown that one mechanism of the neuroprotection involves the secretion of platelet-derived growth factor (PDGF) by MSCs. In this article, Osborne et al. test whether MSCs and/or PDGF confer a similar protection upon human retinas. To study human RGC cell death, the authors took advantage of an explant model in which retinas were isolated from human donor eyes. After being cultured ex vivo for one week, multiple retinal cells, including RGCs, undergo cell death. As in the rodent model, treatment of human retinal explants with PDGF reduced RGC loss and was associated with the activation of various pro-survival pathways, including Akt and ERK.

Together these results suggest that MSCs are likely producing other soluble neuroprotective factors, in addition to PDGF

Interestingly, coculture with MSCs had a more robust neuroprotective phenotype than PDGF treatment and the effect of MSCs was not blocked by inhibition of PDGF. Together these results suggest that MSCs are likely producing other soluble neuroprotective factors, in addition to PDGF. In order to evaluate the safety of this approach, the authors looked at glial/microglial activation and found that both PDGF and MSC coculture induced neuroinflammation. Future work will almost certainly focus on identifying the other neuroprotective agents produced by MSCs and on anti-inflammatory strategies that might permit the use of MSCs therapeutically.

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