Hypoimmunogenic human pluripotent stem cells are valid cell sources for cell therapeutics with normal self-renewal and multilineage differentiation capacity.
Stem Cell Res Ther
; 14(1): 11, 2023 01 24.
Article
in En
| MEDLINE
| ID: mdl-36691086
ABSTRACT
Hypoimmunogenic human pluripotent stem cells (hPSCs) are expected to serve as an unlimited cell source for generating universally compatible "off-the-shelf" cell grafts. However, whether the engineered hypoimmunogenic hPSCs still preserve their advantages of unlimited self-renewal and multilineage differentiation to yield functional tissue cells remains unclear. Here, we systematically studied the self-renewal and differentiation potency of three types of hypoimmunogenic hPSCs, established through the biallelic lesion of B2M gene to remove all surface expression of classical and nonclassical HLA class I molecules (B2Mnull), biallelic homologous recombination of nonclassical HLA-G1 to the B2M loci to knockout B2M while expressing membrane-bound ß2m-HLA-G1 fusion proteins (B2MmHLAG), and ectopic expression of soluble and secreted ß2m-HLA-G5 fusion proteins in B2MmHLAG hPSCs (B2Mm/sHLAG) in the most widely used WA09 human embryonic stem cells. Our results showed that hypoimmunogenic hPSCs with variable expression patterns of HLA molecules and immune compromising spectrums retained their normal self-renewal capacity and three-germ-layer differentiation potency. More importantly, as exemplified by neurons, cardiomyocytes and hepatocytes, hypoimmunogenic hPSC-derived tissue cells were fully functional as of their morphology, electrophysiological properties, macromolecule transportation and metabolic regulation. Our findings thus indicate that engineered hypoimmunogenic hPSCs hold great promise of serving as an unlimited universal cell source for cell therapeutics.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pluripotent Stem Cells
/
Human Embryonic Stem Cells
Limits:
Humans
Language:
En
Journal:
Stem Cell Res Ther
Year:
2023
Document type:
Article
Affiliation country:
China