Injection of Wild Type Embryonic Stem Cells into Mst1 Transgenic Blastocysts Prevents Adult-Onset Cardiomyopathy

Qingshi Zhao, Amanda J. Beck, Joseph M. Vitale, Joel S. Schneider, Corey Chang, Shumin Gao, Dominic del Re, Mantu Bhaumik, Ghassan Yehia, Junichi Sadoshima, Diego Fraidenraich

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Embryonic stem cells have the capacity to differentiate into a wide range of cell types. We previously described that blastocyst injection of wild type (WT) embryonic stem cells (ESCs) into various knockout (KO) mouse models of human disease prevents disease from occurring. In this study we ask if the blastocyst approach can also correct defects in a mouse model of transgenic (Tg) overexpression of a pro-apoptotic factor. We injected ROSA26 (LacZ-marked) WT ESCs into human mammalian sterile 20 like-kinase 1 (Mst1) Tg blastocysts. Mst1 Tg mice overexpress Mst1, a pro-apoptotic factor, in a cardiac-specific manner. As a result, Mst1 Tg mice develop adult dilated cardiomyopathy driven by apoptosis, reduction in cell density and no hypertrophic compensation. Incorporation of WT ESCs generated WT/Mst1 chimeric mice with normal hearts at histological and functional levels. Accordingly, apoptosis and cell density parameters were normalized. The experiments suggest that an adult-onset cardiac myopathy induced by overexpression of the pro-apoptotic Mst1 can be reversed by developmental incorporation of WT ESCs. The findings also suggest that since forced expression of the Mst1 transgene is not abolished in the rescued chimeras, the WT ES-derived cells normalize pathways that lie downstream of Mst1. The results expand the therapeutic capability of the ESCs to mouse models that overproduce detrimental proteins.

Original languageEnglish (US)
Pages (from-to)326-330
Number of pages5
JournalStem Cell Reviews and Reports
Volume7
Issue number2
DOIs
StatePublished - Jun 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Cancer Research

Keywords

  • Apoptosis
  • Cardiomyopathy
  • Chimera
  • ESCs
  • Mst1

Fingerprint Dive into the research topics of 'Injection of Wild Type Embryonic Stem Cells into Mst1 Transgenic Blastocysts Prevents Adult-Onset Cardiomyopathy'. Together they form a unique fingerprint.

Cite this