In Vitro and In Vivo Proteomic Comparison of Human Neural Progenitor Cell‐Induced Photoreceptor Survival

Abstract

Retinal degenerative diseases lead to blindness with few treatments. Various cell‐based therapies are aimed to slow the progression of vision loss by preserving light‐sensing photoreceptor cells. A subretinal injection of human neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) rat model of retinal degeneration has aided in photoreceptor survival, though the mechanisms are mainly unknown. Identifying the retinal proteomic changes that occur following hNPC treatment leads to better understanding of neuroprotection. To mimic the retinal environment following hNPC injection, a co‐culture system of retinas and hNPCs is developed. Less cell death occurs in RCS retinal tissue co‐cultured with hNPCs than in retinas cultured alone, suggesting that hNPCs provide retinal protection in vitro. Comparison of ex vivo and in vivo retinas identifies nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) mediated oxidative response signaling as an hNPC‐induced pathway. This is the first study to compare proteomic changes following treatment with hNPCs in both an ex vivo and in vivo environment, further allowing the use of ex vivo modeling for mechanisms of retinal preservation. Elucidation of the protein changes in the retina following hNPC treatment may lead to the discovery of mechanisms of photoreceptor survival and its therapeutic for clinical applications.

Human Mesenchymal Stem Cell Secretome Exhibits a Neuroprotective Effect over In Vitro Retinal Photoreceptor Degeneration

“…20,24 Our findings suggested that MSCV paracrine properties have a neuroprotective effect in neuroretina against degeneration, results that are in complete agreement with previous reports. 11,25,26 Those studies focused on the evaluation of RGCs or the neuroprotective properties of the human neural progenitor cells (hNPCs); therefore, to the best of our knowledge, this is the first study to evaluate the neuroprotective potential of human bone marrow MSCs over the retinal photoreceptor layer. Our results showed that the immunoexpression levels of PNA lectin, Rho, and PKCa proteins were similar in the neuroretinas co-cultured with MSCVs for 72 h and in the fresh neuroretinas, which may have resulted from the MSCV neuroprotective effect over cones, rods, and rod bipolar cells.…”

“…These results agreed with those reported previously in organ retinal explant cultures, which determined that hNPCs slow the spontaneous photoreceptor degenerative process. 25,26 hNPCs are a type of embryonic stem cell associated with ethical and political controversies. Human MSCs could be the best option for cell therapy strategies because their use does not present ethical problems and they are immunoprivileged 14 or immune evasive.…”

Retinal Neuroprotective Effect of Mesenchymal Stem Cells Secretome Through Modulation of Oxidative Stress, Autophagy, and Programmed Cell Death

“…The current findings suggested that human bmMSC secretome exhibited a neuroprotective effect over in vitro retinal neurodegeneration, which agreed with previous reports. 11 , 12 , 32 , 33 In this sense, it has been reported that retinal neuroprotection may be a consequence of the paracrine properties of the MSC. 5 , 10 – 12 …”

A Stem Cell Journey in Ophthalmology: From the Bench to the Clinic

“… 13 Intriguingly, these cells exhibit RPE‐like behavior. They not only secrete trophic factors that support PR, 14 but also phagocytose rod outer segments, a key function of the RPE. 13 In preclinical models of retinal degeneration, subretinally delivered CNS10‐NPC preserve PRs and vision.…”