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Shaomei Wang, Bin Lu, Sergey Girman, changqing Zhang, Melissa Jones, Zhaohui Chen, Benjamin Bakondi; MSC-Exo as adjuvant potentiate vision preservation following subretinal injection of neural progenitor cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5010.
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© ARVO (1962-2015); The Authors (2016-present)
Neural progenitor cells (NPCs) derived from fetal cortex or iPSC offer great vision protection following subretinal injection into animal models for retinal degeneration. Further, we have shown that combined treatments-subretinal injection of NPCs and intravenous infusion of bone marrow derived mesenchymal stem cells (MSCs) have a synergetic effect in vision preservation. Accumulating evidence indicates that exosomes derived from MSCs (MSC-Exo) play multimodal rules including anti-inflammation, maintaining tissue homeostasis, diminishing apoptosis, ischemia reperfusion, neuroprotective effect and homing to injured tissue. Here we investigate whether MSC-Exo as adjuvant to subretinal NPC grafts will enhance vision preservation.
NPCs (40K/injection) were injected into the subretinal space of the Royal College Surgeon (RCS) rats at postnatal day (P) 21-23, followed by intravenous infusion MSC-Exo (100µg/injection). Blood samples were collected at several time points. Visual function by optokinetic response (OKR), electroretinography (ERG) and luminance threshold recordings (LTR) were examined at P60 and P90. Animals were not immunosuppressed. Histological correlation with visual function were performed at the end of experiment.
MSC-Exo as adjuvant potentiated both photoreceptor and visual function preservation following subretinal injection of NPCs. Visual function tested by OKR, ERG and LTR was significantly better in animals received combined treatment than NPC alone or controls. Photoreceptor preservation and inner retinal connection were also better in combined treated group than controls. Proteomic analysis from blood samples revealed that anti-apoptosis, anti-inflammatory and pro-survival related pathways were increased.
The combined approach enhances vision preservation. Compared with its parent MSCs, exosomes have a superior safety profile, they do not replicate or induce microvascular embolism and can be safely stored without losing function. MSC-Exo might serve as a universal adjuvant to improve clinical outcomes for cell-based therapies.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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