Abstract
Purpose :
Most cell therapy technologies lack the ability to localize cells to their correct target. Subretinal injection of stem cell derived-RPE cells is being evaluated in phase I/II clinical trials for geographic atrophy (GA). The success of this approach is dependent on the identity of the cells injected, and their ability to be delivered to and retained at their target location. Here we evaluate the feasibility of using magnetic cell delivery to enhance iPSC-RPE cell transplant for the treatment of GA.
Methods :
Induced pluripotent stem cells (Infinity Biologic #5200) were differentiated into retinal pigment epithelial (RPE) cells (iPSC-RPE) and labeled using magnetic nanoparticles. Viability and cell identity of magnetic RPE cells were evaluated by flow cytometry using markers for mature RPE and retinal progenitor cells. Labeling efficiency was quantified and magnetic iPSC-RPE cells were selected using a magnetic column.
Magnetic iPSC-RPE cells were labeled with FITC-DEAE-Dextran, and cells were transplanted using a 25G/38G cannula into the subretinal space of freshly harvested rabbit eyes. A neodymium magnet was positioned on the opposite side of the choroid for 2 sec to 2 min to facilitate cell localization, after which the bleb was aspirated. The eyes were fixed in 4% paraformaldehyde, and retinas and Bruch’s membrane were imaged to confirm distribution and retention of the magnetic iPSC-RPE cells using an anti-human CD166-PE or magnetic particle-specific antibody.
Results :
At harvesting, iPSC-RPE cells were >85% viable and positive for identity markers BEST1, RPE65 and CD56. Labeling these cells with magnetic nanoparticles did not affect viability or identity. Magnetic selection recovered ~95% of the cells, indicating high labeling efficiency. Subretinal injection of magnetic RPE cells in combination with an external magnetic force significantly improved retention and distribution of the donor cells.
Conclusions :
Magnetic cell delivery of iPSC-RPE cells may be an effective technique for improving retention and distribution of RPE cells in the subretinal space and lead to better vision restoration in geographic atrophy.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.