Abstract
BackgroundOptic-nerve injury results in impaired transmission of visual signals to central targets and leads to the death of retinal ganglion cells (RGCs) and irreversible vision loss. Therapies with mesenchymal stem cells (MSCs) from different sources have been used experimentally to increase survival and regeneration of RGCs.MethodsWe investigated the efficacy of human umbilical Wharton’s jelly-derived MSCs (hWJ-MSCs) and their extracellular vesicles (EVs) in a rat model of optic nerve crush.ResultshWJ-MSCs had a sustained neuroprotective effect on RGCs for 14, 60, and 120 days after optic nerve crush. The same effect was obtained using serum-deprived hWJ-MSCs, whereas transplantation of EVs obtained from those cells was ineffective. Treatment with hWJ-MSCs also promoted axonal regeneration along the optic nerve and reinnervation of visual targets 120 days after crush.ConclusionsThe observations showed that this treatment with human-derived MSCs promoted sustained neuroprotection and regeneration of RGCs after optic nerve injury. These findings highlight the possibility to use cell therapy to preserve neurons and to promote axon regeneration, using a reliable source of human MSCs.
Highlights
Optic-nerve injury results in impaired transmission of visual signals to central targets and leads to the death of retinal ganglion cells (RGCs) and irreversible vision loss
Since clinical protocols require that cell therapy be performed in xeno-free conditions [51], we evaluated if serum deprivation affects the neuroprotective potential of hWJ-mesenchymal stem cells (MSCs)
We found that there was no statistically significant effect of the presence or absence of serum on the neuroprotective effect, the mean number of surviving RGCs treated with hWJ-MSCs cultured in the presence of serum was higher compared to SD-hWJ-MSCs (338.5 ± 25.00 Tuj1+ cells/mm2; Fig. 1D, F)
Summary
Optic-nerve injury results in impaired transmission of visual signals to central targets and leads to the death of retinal ganglion cells (RGCs) and irreversible vision loss. Therapies with mesenchymal stem cells (MSCs) from different sources have been used experimentally to increase survival and regeneration of RGCs. Methods: We investigated the efficacy of human umbilical Wharton’s jelly-derived MSCs (hWJ-MSCs) and their extracellular vesicles (EVs) in a rat model of optic nerve crush. Optic nerve injuries resulting from optic neuropathies, traumas, or tumors are characterized by optic nerve degeneration, resulting in partial to complete loss of vision [1]. Optic nerve injury interrupts the connection with axonal targets such as the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC), which results in failure in shuttling trophic factors [3, 23, 24]
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