TY - JOUR
T1 - IPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats
T2 - A Follow-Up Study
AU - Westenskow, Peter D.
AU - Bucher, Felicitas
AU - Bravo, Stephen
AU - Kurihara, Toshihide
AU - Feitelberg, Daniel
AU - Paris, Liliana P.
AU - Aguilar, Edith
AU - Lin, Jonathan H.
AU - Friedlander, Martin
N1 - Funding Information:
The authors wish to acknowledge assistance from Drs. Lea Scheppke and Alan Bird for critically evaluating the paper. They also acknowledge technical assistance from Dr. Malcolm R. Wood at the EM Core Facility, Michele Courtney in the TSRI Pathology Lab, and Dr. Shari Hamilton at IDEXX RADIL. This work was funded by grants from The California Institute of Regenerative Medicine (CIRM TR1- 01219) and The Lowy Medical Research Institute to Martin Friedlander and from the National Eye Institute to Martin Friedlander (EY11254) and Jonathan H. Lin (EY020846) and by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award EY021416 to Peter D.Westenskow.
Publisher Copyright:
© 2016 Peter D. Westenskow et al.
PY - 2016
Y1 - 2016
N2 - Phototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE) cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD), a very common neurodegenerative disease for which no cure exists. RPE replacement is a promising therapeutic intervention for AMD, and large numbers of RPE cells can be generated from pluripotent stem cells. However, questions persist regarding iPSC-derived RPE (iPS-RPE) viability, immunogenicity, and tumorigenesis potential. We showed previously that iPS-RPE prevent photoreceptor atrophy in dystrophic rats up until 24 weeks after implantation. In this follow-up study, we longitudinally monitored the same implanted iPS-RPE, in the same animals. We observed no gross abnormalities in the eyes, livers, spleens, brains, and blood in aging rats with iPSC-RPE grafts. iPS-RPE cells that integrated into the subretinal space outlived the photoreceptors and survived for as long as 2 1/2 years while nonintegrating RPE cells were ingested by host macrophages. Both populations could be distinguished using immunohistochemistry and electron microscopy. iPSC-RPE could be isolated from the grafts and maintained in culture; these cells also phagocytosed isolated photoreceptor outer segments. We conclude that iPS-RPE grafts remain viable and do not induce any obvious associated pathological changes.
AB - Phototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE) cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD), a very common neurodegenerative disease for which no cure exists. RPE replacement is a promising therapeutic intervention for AMD, and large numbers of RPE cells can be generated from pluripotent stem cells. However, questions persist regarding iPSC-derived RPE (iPS-RPE) viability, immunogenicity, and tumorigenesis potential. We showed previously that iPS-RPE prevent photoreceptor atrophy in dystrophic rats up until 24 weeks after implantation. In this follow-up study, we longitudinally monitored the same implanted iPS-RPE, in the same animals. We observed no gross abnormalities in the eyes, livers, spleens, brains, and blood in aging rats with iPSC-RPE grafts. iPS-RPE cells that integrated into the subretinal space outlived the photoreceptors and survived for as long as 2 1/2 years while nonintegrating RPE cells were ingested by host macrophages. Both populations could be distinguished using immunohistochemistry and electron microscopy. iPSC-RPE could be isolated from the grafts and maintained in culture; these cells also phagocytosed isolated photoreceptor outer segments. We conclude that iPS-RPE grafts remain viable and do not induce any obvious associated pathological changes.
UR - http://www.scopus.com/inward/record.url?scp=84956623199&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84956623199&partnerID=8YFLogxK
U2 - 10.1155/2016/8470263
DO - 10.1155/2016/8470263
M3 - Article
AN - SCOPUS:84956623199
SN - 1687-966X
VL - 2016
JO - Stem Cells International
JF - Stem Cells International
M1 - 8470263
ER -