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Blastocyst Injection of Embryonic Stem Cells: A Simple Approach to Unveil Mechanisms of Corrections in Mouse Models of Human Disease

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Abstract

Embryonic stem cell (ESC) research is a promising area of investigation with enormous therapeutic potential. We have injected murine wild type (WT) ESCs into a variety of mutant murine blastocysts, which are predisposed to develop a human-like disease, such as muscular dystrophy or the embryonic lethal “thin myocardial syndrome”. In this review, we summarize data indicating that partial incorporation of ESCs is sufficient to prevent disease from occurring. We also present data indicating that blastocyst incorporation of ESCs may aid in the prevention of heart failure in stressed WT mice. In some cases, the rescue observed is predominantly non-cell autonomous and relies on the production of secreted factors from the ES-derived cells, but in others, cell replacement is required. Thus, congenital or acquired disease can be pre-emptively averted in mice by developmental injection of ESCs.

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Acknowledgments

We thank Dr. Robert Benezra (Memorial Sloan-Kettering Cancer Center) for support with initial studies. This work was supported by the National Institutes of Health (D.F., A.T.), American Heart Association (D.F.), Muscular Dystrophy Association (D.F.), New Jersey Commission on Science and Technology (D.F.), UMDNJ Foundation (D.F.), American Society for Clinical Pharmacology and Therapeutics (A.T.), Marriott Heart Disease Research Program (A.T.), Marriott Foundation (A.T.), Ted Nash Long Life Foundation (A.T.), Ralph Wilson Medical Research Foundation (A.T.), and Mayo Clinic Clinician-Investigator Program (A.T.).

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Authors and Affiliations

  1. Department of Cell Biology and Molecular Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Ave MSB G-609, Newark, NJ, 07107, USA

    Joel S. Schneider, Joseph M. Vitale & Diego Fraidenraich

  2. Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN, USA

    Andre Terzic

Authors
  1. Joel S. Schneider
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  2. Joseph M. Vitale
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  3. Andre Terzic
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  4. Diego Fraidenraich
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Correspondence to Diego Fraidenraich.

Additional information

Joel S. Schneider and Joseph M. Vitale contributed equally to this work

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Schneider, J.S., Vitale, J.M., Terzic, A. et al. Blastocyst Injection of Embryonic Stem Cells: A Simple Approach to Unveil Mechanisms of Corrections in Mouse Models of Human Disease. Stem Cell Rev and Rep 5, 369–377 (2009). https://doi.org/10.1007/s12015-009-9089-6

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  • DOI: https://doi.org/10.1007/s12015-009-9089-6

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