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Sehwon Koh, Namsoo Kim, Nadine S Dejneka, Ian R Harris, Henry H Yin, Cagla Eroglu; Human umbilical tissue-derived cells (hUTC) promote synapse formation and neurite outgrowth via Thrombospondin family proteins: A potential mechanism for hUTC-based therapy in retinal-degenerative diseases. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2258.
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© ARVO (1962-2015); The Authors (2016-present)
Human umbilical tissue-derived cells (hUTC) were previously shown to preserve vision in a rodent model of retinal degeneration; however, it is not clear how the cells were able to achieve this effect. We hypothesize that hUTC may improve vision by promoting neuronal survival, neurite outgrowth and synaptogenesis.
We utilized a purified rat retinal ganglion cell (RGC) culture system. In this in vitro system we studied the effects of hUTC-conditioned media on RGC survival, neurite outgrowth and synapse formation.
We found that hUTC promote neuronal survival and enhance neurite outgrowth. Interestingly, hUTC strongly induce excitatory synaptogenesis between RGCs as determined by immunolabeling of synaptic markers and electrophysiological recordings. The synaptogenic factors are larger than 100kDa and can be blocked by the antiepileptic drug Gabapentin. Gabapentin is a known blocker of synaptogenic Thrombospondin (TSP) family proteins. We found that hUTC secrete TSPs (TSP1, 2 and 4) and silencing TSP expression in hUTC eliminated the synaptogenic effects of these cells as well as their ability to promote neurite outgrowth.
Our results show hUTC enhance neuronal survival, neurite outgrowth and promote development of functional synapses through trophic mechanisms. We identified TSPs as the major synaptogenic factors secreted by hUTC. hUTC-secreted TSPs also supported neurite outgrowth. Our findings demonstrate that hUTC affect multiple aspects of retinal cell health and connectivity and each of these paracrine effects may individually contribute to the therapeutic function of these cells.
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