Cardiac engraftment of genetically-selected parthenogenetic stem cell-derived cardiomyocytes

PLoS One. 2015 Jun 25;10(6):e0131511. doi: 10.1371/journal.pone.0131511. eCollection 2015.

Abstract

Parthenogenetic stem cells (PSCs) are a promising candidate donor for cell therapy applications. Similar to embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), PSCs exhibit self-renewing capacity and clonogenic proliferation in vitro. PSCs exhibit largely haploidentical genotype, and as such may constitute an attractive population for allogenic applications. In this study, PSCs isolated from transgenic mice carrying a cardiomyocyte-restricted reporter transgene to permit tracking of donor cells were genetically modified to carry a cardiomyocyte-restricted aminoglycoside phosphotransferase expression cassette (MHC-neor/pGK-hygror) to permit the generation of highly enriched cardiomyocyte cultures from spontaneously differentiating PSCs by simple selection with the neomycin analogue G148. Following engraftment into isogenic recipient hearts, the selected cardiomyocytes formed a functional syncytium with the host myocardium as evidenced by the presence of entrained intracellular calcium transients. These cells thus constitute a potential source of therapeutic donor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cell Transplantation / methods
  • Electroporation
  • Female
  • Genotype
  • Green Fluorescent Proteins / metabolism
  • Kanamycin Kinase / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Myocardium / metabolism
  • Myocytes, Cardiac / cytology*
  • Parthenogenesis
  • Polymerase Chain Reaction
  • Stem Cells / cytology*
  • Transfection
  • Transgenes

Substances

  • Green Fluorescent Proteins
  • Kanamycin Kinase