Compensation of Disabled Organogeneses in Genetically Modified Pig Fetuses by Blastocyst Complementation

Stem Cell Reports. 2020 Jan 14;14(1):21-33. doi: 10.1016/j.stemcr.2019.11.008. Epub 2019 Dec 26.

Abstract

We have previously established a concept of developing exogenic pancreas in a genetically modified pig fetus with an apancreatic trait, thereby proposing the possibility of in vivo generation of functional human organs in xenogenic large animals. In this study, we aimed to demonstrate a further proof-of-concept of the compensation for disabled organogeneses in pig, including pancreatogenesis, nephrogenesis, hepatogenesis, and vasculogenesis. These dysorganogenetic phenotypes could be efficiently induced via genome editing of the cloned pigs. Induced dysorganogenetic traits could also be compensated by allogenic blastocyst complementation, thereby proving the extended concept of organ regeneration from exogenous pluripotent cells in empty niches during various organogeneses. These results suggest that the feasibility of blastocyst complementation using genome-edited cloned embryos permits experimentation toward the in vivo organ generation in pigs from xenogenic pluripotent cells.

Keywords: blastocyst complementation; cloned pig; organ regeneration; organogenesis; pluripotent stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Biomarkers
  • Blastocyst / cytology*
  • Blastocyst / metabolism*
  • Cell Differentiation* / genetics
  • Cloning, Organism
  • Fetus
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Homeodomain Proteins
  • Organogenesis* / genetics
  • Pancreas / embryology
  • Phenotype
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Regeneration
  • Swine
  • Trans-Activators / deficiency

Substances

  • Biomarkers
  • Homeodomain Proteins
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein