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Immunological aspects of RPE cell transplantation.
Prog Retin Eye Res. 2021 Jan 19 [Online ahead of print]PR

Abstract

Retinal pigment epithelial (RPE) cells have several functions, including support of the neural retina and choroid in the eye and immunosuppression. Cultured human RPE cells directly suppress inflammatory immune cells. For instance, they directly suppress the activation of T cells in vitro. In contrast, transplanted allogeneic human RPE cells are rejected by bystander immune cells such as T cells in vivo. Recently, human embryonic stem cell-derived RPE cells have been used in several clinical trials, and human induced pluripotent stem cell (iPSC)-RPE cells have also been tested in our clinical study in patients with retinal degeneration. Major safety concerns after stem cell-based transplantation surgery include hyper-proliferation, tumorigenicity, or ectopic tissue formation, but these events have currently not been seen in any of these patients. However, if RPE cells are allogeneic, there are concerns about immune rejection issues that have been raised in previous clinical trials. We therefore performed a preclinical study of allogeneic iPSC-RPE cell transplantation in animal rejection models. We then conducted autogenic or allogeneic iPSC-RPE cell transplantation in clinical studies of patients with age-related macular degeneration. In this review, we focus on immunological studies of RPE cells, including iPSC-derived cells. iPSC-RPE cells have unique inflammatory (immunosuppressive and immunogenic) characteristics like primary cultured RPE cells. The purpose of this review is to summarize the current findings obtained from preclinical (basic research) and clinical studies in iPSC-RPE cell transplantation, especially the immunological aspects.

Authors+Show Affiliations

Laboratory for Retinal Regeneration, Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research Kobe, Japan; Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan. Electronic address: sunao.sugita@riken.jp.Laboratory for Retinal Regeneration, Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research Kobe, Japan; Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan.Department of Ophthalmology, Kawasaki Medical School, Okayama, Japan.Laboratory for Retinal Regeneration, Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research Kobe, Japan; Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

33482342

Citation

Sugita, Sunao, et al. "Immunological Aspects of RPE Cell Transplantation." Progress in Retinal and Eye Research, 2021, p. 100950.
Sugita S, Mandai M, Kamao H, et al. Immunological aspects of RPE cell transplantation. Prog Retin Eye Res. 2021.
Sugita, S., Mandai, M., Kamao, H., & Takahashi, M. (2021). Immunological aspects of RPE cell transplantation. Progress in Retinal and Eye Research, 100950. https://doi.org/10.1016/j.preteyeres.2021.100950
Sugita S, et al. Immunological Aspects of RPE Cell Transplantation. Prog Retin Eye Res. 2021 Jan 19;100950. PubMed PMID: 33482342.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunological aspects of RPE cell transplantation. AU - Sugita,Sunao, AU - Mandai,Michiko, AU - Kamao,Hiroyuki, AU - Takahashi,Masayo, Y1 - 2021/01/19/ PY - 2020/09/28/received PY - 2021/01/04/revised PY - 2021/01/11/accepted PY - 2021/1/23/pubmed PY - 2021/1/23/medline PY - 2021/1/22/entrez KW - Age-related macular degeneration KW - Immune rejection KW - Retinal pigment epithelial cells KW - Stem cells KW - Transplantation SP - 100950 EP - 100950 JF - Progress in retinal and eye research JO - Prog Retin Eye Res N2 - Retinal pigment epithelial (RPE) cells have several functions, including support of the neural retina and choroid in the eye and immunosuppression. Cultured human RPE cells directly suppress inflammatory immune cells. For instance, they directly suppress the activation of T cells in vitro. In contrast, transplanted allogeneic human RPE cells are rejected by bystander immune cells such as T cells in vivo. Recently, human embryonic stem cell-derived RPE cells have been used in several clinical trials, and human induced pluripotent stem cell (iPSC)-RPE cells have also been tested in our clinical study in patients with retinal degeneration. Major safety concerns after stem cell-based transplantation surgery include hyper-proliferation, tumorigenicity, or ectopic tissue formation, but these events have currently not been seen in any of these patients. However, if RPE cells are allogeneic, there are concerns about immune rejection issues that have been raised in previous clinical trials. We therefore performed a preclinical study of allogeneic iPSC-RPE cell transplantation in animal rejection models. We then conducted autogenic or allogeneic iPSC-RPE cell transplantation in clinical studies of patients with age-related macular degeneration. In this review, we focus on immunological studies of RPE cells, including iPSC-derived cells. iPSC-RPE cells have unique inflammatory (immunosuppressive and immunogenic) characteristics like primary cultured RPE cells. The purpose of this review is to summarize the current findings obtained from preclinical (basic research) and clinical studies in iPSC-RPE cell transplantation, especially the immunological aspects. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/33482342/Immunological_aspects_of_RPE_cell_transplantation. L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(21)00011-2 DB - PRIME DP - Unbound Medicine ER -
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