In:
Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-7-22)
Kurzfassung:
Universally acceptable donor cells have been developed to address the unmet need for immunotypically matched materials for regenerative medicine. Since forced expression of hypoimmunogenic genes represses the immune response, we established universal pluripotent stem cells (PSCs) by replacing endogenous β2-microglobulin (β2m) with β2m directly conjugated to human leukocyte antigen (HLA)-G, thereby simultaneously suppressing HLA-I expression and the natural killer (NK) cell-mediated immune response. These modified human PSCs retained their pluripotency and differentiation capacity; however, surface presentation of HLA-G was absent from subsequently differentiated cells, particularly cells of neural lineages, due to the downregulation of antigen processing and presentation machinery (APM) genes. Induction of APM genes by overexpression of NLR-family CARD domain-containing 5 (NLRC5) or activator subunit of nuclear factor kappa B (NF-κB) heterodimer (RelA) recovered the surface expression of HLA-G and the hypoimmunogenicity of neural cells. Our findings enhance the utility of hypoimmunogenic cells as universal donors and will contribute to the development of off-the-shelf stem-cell therapeutics.
Materialart:
Online-Ressource
ISSN:
2296-4185
DOI:
10.3389/fbioe.2022.936584
DOI:
10.3389/fbioe.2022.936584.s001
DOI:
10.3389/fbioe.2022.936584.s002
DOI:
10.3389/fbioe.2022.936584.s003
DOI:
10.3389/fbioe.2022.936584.s004
DOI:
10.3389/fbioe.2022.936584.s005
DOI:
10.3389/fbioe.2022.936584.s006
DOI:
10.3389/fbioe.2022.936584.s007
DOI:
10.3389/fbioe.2022.936584.s008
DOI:
10.3389/fbioe.2022.936584.s009
Sprache:
Unbekannt
Verlag:
Frontiers Media SA
Publikationsdatum:
2022
ZDB Id:
2719493-0
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