Rescue of developmental defects by blastocyst stem cell injection: Towards elucidation of neomorphic corrective pathways

Qingshi Zhao, Amanda Beck, Joseph M. Vitale, Joel S. Schneider, Andre Terzic, Diego Fraidenraich

Research output: Contribution to journalReview article

3 Scopus citations

Abstract

Stem cell-based therapy is an exciting area of high potential for regenerative medicine. To study disease prevention, we inject mouse embryonic stem cells (ESCs) into a variety of mouse blastocysts, most of which harbor mutations. Mice derived from these mutant blastocysts develop human-like diseases, either at developmental stages or in the adult, but blastocyst injection of ESCs prevents disease from occurring. Rather than entirely repopulating the affected organs, with just 20% of chimerism, the ESCs replenish protein levels that are absent in mutant mice, and induce novel or "neomorphic" signals that help circumvent the requirements for the mutations. We also show data indicating that the "neomorphic" mechanisms arise as a result of blastocyst injection of ESCs, regardless of the nature of the host blastocyst (mutant or wild-type). Thus, blastocyst injection of ESCs not only allows the study of disease prevention, but also unveils novel pathways whose activation may aid in the correction of congenital or acquired disease.

Original languageEnglish (US)
Pages (from-to)66-72
Number of pages7
JournalJournal of cardiovascular translational research
Volume3
Issue number1
DOIs
StatePublished - Feb 2010

Keywords

  • Blastocyst
  • Congenital Heart Disease
  • Embryonic Stem Cells
  • Mouse Model of Human Disease
  • Muscular Dystrophy
  • Myocardial Infarction
  • Neomorphic Effects

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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