TY - JOUR
T1 - Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression
AU - Liu, Zengping
AU - Parikh, Bhav Harshad
AU - Tan, Queenie Shu Woon
AU - Wong, Daniel Soo Lin
AU - Ong, Kok Haur
AU - Yu, Weimiao
AU - Seah, Ivan
AU - Holder, Graham E.
AU - Hunziker, Walter
AU - Tan, Gavin S.W.
AU - Barathi, Veluchamy Amutha
AU - Lingam, Gopal
AU - Stanzel, Boris V.
AU - Blenkinsop, Timothy A.
AU - Su, Xinyi
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/2/9
Y1 - 2021/2/9
N2 - Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy. In this article, Su and colleagues show that hRPESC-RPE transplanted under the macula of non-human primates was able to integrate with host retina, recover RPE-specific markers, and support photoreceptor function. Importantly, transplanted grafts did not undergo epithelial-mesenchymal transition and gliosis was not observed in adjacent retina. Thus, hRPESC-RPE may be a useful source for RPE cell replacement therapy.
AB - Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy. In this article, Su and colleagues show that hRPESC-RPE transplanted under the macula of non-human primates was able to integrate with host retina, recover RPE-specific markers, and support photoreceptor function. Importantly, transplanted grafts did not undergo epithelial-mesenchymal transition and gliosis was not observed in adjacent retina. Thus, hRPESC-RPE may be a useful source for RPE cell replacement therapy.
KW - Macaca fascicularis
KW - age-related maculopathy
KW - cell transplantation
KW - epithelial-mesenchymal transition
KW - photoreceptor cells
KW - retinal pigment epithelium
UR - http://www.scopus.com/inward/record.url?scp=85100429489&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2020.12.007
DO - 10.1016/j.stemcr.2020.12.007
M3 - Article
C2 - 33450191
AN - SCOPUS:85100429489
SN - 2213-6711
VL - 16
SP - 237
EP - 251
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 2
ER -