Embryonic stem cells prevent developmental cardiac defects in mice.
The potential therapeutic use of embryonic stem cells (ESCs) has gathered the attention of the scientific and medical communities recently. We report that in addition to their unique capacity to populate defective cardiac tissues, ESCs secrete factors that correct gene expression profiles in the defective neighboring cells. Id (inhibitor of DNA binding) gene knockout (KO) mouse embryos die at midgestation because of multiple cardiac defects, but injection of ESCs into preimplantation Id KO embryos prevents these defects and corrects gene expression profiles throughout the heart. ESCs injected into expectant mothers only partially rescue cardiac defects in the Id KO embryos. Two secreted factors are implicated in the rescue process: insulin-like growth factor I accounts for the long-range action of the ESCs, and Wnt5a, a short-range factor, corrects gene expression profiles in the Id KO hearts. Future studies are discussed.
Fraidenraich
Diego
D
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. fraidend@mskcc.org
Benezra
Robert
R
D000818:Animals; D004622:Embryo, Mammalian; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006330:Heart Defects, Congenital / Q000196:embryology* / Q000517:prevention & control; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein
D051796:Inhibitor of Differentiation Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D007334:Insulin-Like Growth Factor I