Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression

Autor: Queenie Shu Woon Tan, Gavin Tan, Boris V. Stanzel, Veluchamy A Barathi, Daniel Soo Lin Wong, Zengping Liu, Kok Haur Ong, Graham E. Holder, Walter Hunziker, Weimiao Yu, Timothy A. Blenkinsop, Gopal Lingam, Xinyi Su, Ivan Seah, Bhav Harshad Parikh
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Pathology
genetic structures
medicine.medical_treatment
retinal pigment epithelium
photoreceptor cells
Biochemistry
Macular Degeneration
0302 clinical medicine
Cells
Cultured
Aged
80 and over
Immunosuppression
medicine.anatomical_structure
age-related maculopathy
Heterografts
Female
Stem cell
medicine.symptom
Primates
medicine.medical_specialty
Epithelial-Mesenchymal Transition
Biology
Retina
Article
03 medical and health sciences
Genetics
medicine
Animals
Humans
cell transplantation
Aged
Cell Proliferation
Immunosuppression Therapy
Retinal pigment epithelium
Cell Biology
Macular degeneration
medicine.disease
eye diseases
Transplantation
Age-related maculopathy
Disease Models
Animal
Macaca fascicularis
030104 developmental biology
Gliosis
sense organs
030217 neurology & neurosurgery
Developmental Biology
Stem Cell Transplantation
Zdroj: Stem Cell Reports
ISSN: 2213-6711
Popis: Summary 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.
Highlights • hRPESC-RPE monolayer transplanted under macula of non-human primates • Transplanted hRPESC-RPE recovers in vivo and maintains healthy photoreceptors • Transplanted cells did not undergo epithelial-mesenchymal transition • Gliosis was not observed in adjacent retina for up to at least 3 months
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.
Databáze: OpenAIRE
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