Stem Cell Regenerative Medicine: Lessons from Animal Models?
Kluas Ingo Matthaei, Ph.D
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Chair, Adjunct Professor Stem Cell Unit, Anatomy Department College of Medicine and King Saud University Riyadh, Saudi Arabia
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Division of Molecular Bioscience The John Curtin School of Medical Research ANU College of Medicine, Biology and Environment The Australian National University Canberra, ACT 0200 Australia
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Abstract
The discovery of embryonic stem (ES) cells allowing the generation of gene deficient mice in combination with DNA injections into single cell embryos to generate transgenic mice has revolutionized our ability to dramatically improve our understanding of gene function in vivo. Importantly the discovery of ES (then induced Pluripotent Stem [iPS] cell has demonstrated their pluripotency and the potential to use these cells in regenerative medicine for the treatment of human diseases. Indeed the ability to generate pluripotent cells from individual patients by therapeutic cloning, which might include genetic modification, may well become a reality. However, it is now becoming clear that in the mouse the same genetic modification (either gene deficient or transgenic) can have a very different phenotype when made in different genetic backgrounds (Matthaei 2004, 2007, 2009) often producing serious even lethal outcomes. Given the dramatic genetic variation in the human population, routine modifications may therefore be unpredictable. Caveats of current procedures will be discussed.
Matthaei KI (2004)
Caveats of Gene Targeted and Transgenic Mice in Handbook of Stem Cells, Volume 1: Embryonic Stem Cells, Elsevier Academic Press, (Lanza R et. al. ed) pp589-598
Matthaei KI (2007)
Genetically manipulated mice: A powerful tool with unsuspected caveats The Journal of Physiology 582, 481-488.
Matthaei KI (2009)
Identification of Therapeutic Drug Targets through Genetically Manipulated Mice: Are We Getting it Right? Pharmacology and Therapeutics, 123, 32-36