Humanized skeletal muscle in MYF5/MYOD/MYF6-null pig embryos.

Autor: Maeng G; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA., Das S; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA., Greising SM; School of Kinesiology, University of Minnesota, Minneapolis, MN, USA., Gong W; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA., Singh BN; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA., Kren S; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA., Mickelson D; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA., Skie E; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA., Gafni O; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA., Sorensen JR; School of Kinesiology, University of Minnesota, Minneapolis, MN, USA., Weaver CV; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA., Garry DJ; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA. garry@umn.edu.; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA. garry@umn.edu.; Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota, Minneapolis, MN, USA. garry@umn.edu.; NorthStar Genomics, Eagan, MN, USA. garry@umn.edu., Garry MG; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA. garry002@umn.edu.; Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota, Minneapolis, MN, USA. garry002@umn.edu.; NorthStar Genomics, Eagan, MN, USA. garry002@umn.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2021 Aug; Vol. 5 (8), pp. 805-814. Date of Electronic Publication: 2021 Mar 29.
DOI: 10.1038/s41551-021-00693-1
Abstrakt: Because post-mortem human skeletal muscle is not viable, autologous muscle grafts are typically required in tissue reconstruction after muscle loss due to disease or injury. However, the use of autologous tissue often leads to donor-site morbidity. Here, we show that intraspecies and interspecies chimaeric pig embryos lacking native skeletal muscle can be produced by deleting the MYF5, MYOD and MYF6 genes in the embryos via CRISPR, followed by somatic-cell nuclear transfer and the delivery of exogenous cells (porcine blastomeres or human induced pluripotent stem cells) via blastocyst complementation. The generated intraspecies chimaeras were viable and displayed normal histology, morphology and function. Human:pig chimaeras generated with TP53-null human induced pluripotent stem cells led to higher chimaerism efficiency, with embryos collected at embryonic days 20 and 27 containing humanized muscle, as confirmed by immunohistochemical and molecular analyses. Human:pig chimaeras may facilitate the production of exogenic organs for research and xenotransplantation.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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