Transplantation of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in a Swine Model of Geographic Atrophy

Abstract

Background: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). Methods: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. Results: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. Conclusions: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA.

Customized strategies for high-yield purification of retinal pigment epithelial cells differentiated from different stem cell sources

“…By week 10, the TEER for RPE derived from the different purification techniques were similar and exceeded 300 Ω cm 2 , consistent with previously reported values for stem cell derived RPE (Fig. 4 d) 26 , 27 . As expected, the TEER was negligible in weakly adherent cells after TrypLE treatment and in SSC low fractions, indicating that they did not contain many RPE (or other epithelial) cells.…”

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development

“…The transplanted retinal organoid survived for seven months and showed good integration into the host [ 147 ]. Recently, hiPSC-derived RPE cells injected into an atrophic retina of a swine model showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability [ 148 ]. These results show that hiPSC-RPE can slow down progression of disease [ 148 ].…”

“…Recently, hiPSC-derived RPE cells injected into an atrophic retina of a swine model showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability [ 148 ]. These results show that hiPSC-RPE can slow down progression of disease [ 148 ]. Moreover, the transplantation of combined RPE sheets with retinal sheets in the subretinal segment of RSC rats showed their potential in complete replacement of degenerated retina; this therapy could be used in advanced stages of retinal degeneration [ 149 ].…”

iPSC Therapy for Myocardial Infarction in Large Animal Models: Land of Hope and Dreams

“…Direct iPSC delivery through transplantation or injection has become the most studied approach in regenerative medicine [ 101 , 102 , 103 , 104 , 105 , 106 , 107 ]. However, iPSC translational efforts have been dampened by concerns regarding the teratogenic potential of undifferentiated cells, as well as the lack of timely stimuli to carefully guide the in situ differentiation of these cells [ 108 ].…”