Abstract
Purpose :
There is no effective treatment for retinitis pigmentosa. Studies have shown the potential benefits of using mesenchymal stem cell (MSC) therapies in inherited retinal degeneration (IRD). However, the safety of intraocular injections of MSCs have not been fully explored. This study utilized Royal College of Surgeons (RCS) rats, an innate-born of retinal degeneration, as a model for IRD, and investigated the effects of intraocular injections of human Adipose-derived stem cells (hADSCs).
Methods :
The safety of human ADSCs (hADSCs) was investigated in RCS rats through two different injection methods: subretinal injection (SRI), and subtenon's injection (STI). Daily oral cyclosporine was given. We conducted body weight assessments, autopsies, histopathological exams, and enzyme-linked immunosorbent assay (ELISA) analyses to evaluate the systematic responses. In addition, the treatment effects in retina were gauged through OCT, ERG, and IHC at various intervals up to 56 days.
Results :
Two months after the injections, severe adverse events (SAEs) were found in the rats receiving SRI and STI administrations, such as weakness, growth retard (body weights were decreased significantly in STI and SRI compared with PBS by roughly 35% and 39%, respectively), and death (mortality rate for both STI and SRI is 100%). However, the intravenous injection of hADSCs didn’t trigger any SAE. Autopsy showed that epidermal, follicular and adnexal atrophy in skin, myopathy in skeletal muscle, and pneumonia in lung. ELISA analysis demonstrated that xenograft rejection markers (IL-18, and CXCL-10) in serum were significantly expressed by intraocular injections of hADSCs (p<0.05). IL-18 and CXCL10 were significantly increased in the serum of STI rats on day 7 after treatment compared with PBS (approximately 9-fold and 4-fold, respectively). CD8-positive cells and human HLA-DR-positive cells in the ocular section were found in both STI and SRI groups, but not in the non-treated group.
Conclusions :
Given the impact of innate immune deficits, those utilizing RCS rats for functional readouts of xenografts should be mindful that the resulting data may harmful to induce systemic adverse reactions.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.