Generation of Retinal Pigment Epithelial Cells Derived from Human Embryonic Stem Cells Lacking Human Leukocyte Antigen Class I and II | Zendy

Sandra Petrus-Reurer | Zendy; Nerges Winblad | Zendy; Pankaj Kumar | Zendy; Laia Gorchs | Zendy; Michael Chrobok | Zendy; Arnika Kathleen Wagner | Zendy; Hammurabi Bartuma | Zendy; Emma Lardner | Zendy; Monica Aronsson | Zendy; Álvaro Plaza Reyes | Zendy; Helder André | Zendy; Evren Alici | Zendy; Helen Kaipe | Zendy; Anders Kvanta | Zendy; Fredrik Lanner | Zendy

Open Access

Generation of Retinal Pigment Epithelial Cells Derived from Human Embryonic Stem Cells Lacking Human Leukocyte Antigen Class I and II

Author(s) -

Sandra Petrus-Reurer,

Nerges Winblad,

Pankaj Kumar,

Laia Gorchs,

Michael Chrobok,

Arnika Kathleen Wagner,

Hammurabi Bartuma,

Emma Lardner,

Monica Aronsson,

Álvaro Plaza Reyes,

Helder André,

Evren Alici,

Helen Kaipe,

Anders Kvanta,

Fredrik Lanner

Publication year - 2020

Publication title -

stem cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.207

H-Index - 76

ISSN - 2213-6711

DOI - 10.1016/j.stemcr.2020.02.006

Subject(s) - biology , ciita , embryonic stem cell , cd8 , immunology , human leukocyte antigen , transplantation , antigen , microbiology and biotechnology , major histocompatibility complex , stem cell , cytotoxic t cell , immune system , mhc class ii , in vitro , genetics , medicine , gene

Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells could serve as a replacement therapy in advanced stages of age-related macular degeneration. However, allogenic hESC-RPE transplants trigger immune rejection, supporting a strategy to evade their immune recognition. We established single-knockout beta-2 microglobulin (SKO-B2M), class II major histocompatibility complex transactivator (SKO-CIITA) and double-knockout (DKO) hESC lines that were further differentiated into corresponding hESC-RPE lines lacking either surface human leukocyte antigen class I (HLA-I) or HLA-II, or both. Activation of CD4+ and CD8+ T-cells was markedly lower by hESC-RPE DKO cells, while natural killer cell cytotoxic response was not increased. After transplantation of SKO-B2M, SKO-CIITA, or DKO hESC-RPEs in a preclinical rabbit model, donor cell rejection was reduced and delayed. In conclusion, we have developed cell lines that lack both HLA-I and -II antigens, which evoke reduced T-cell responses in vitro together with reduced rejection in a large-eyed animal model.

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