Chimeric Pigs Produced from Induced Pluripotent Stem Cells

Scientists succeeded in making induced pluripotent stem cells in pigs (Zhao Wu, et al. Generation of Pig Induced Pluripotent Stem Cells with a Drug-Inducible System. J Mol Cell Biol 1, no. 1 (2009): 46-54). Pig iPSCs are a valuable research tool, since pig cells have a greater similarity to humans than do mouse cells. Also, pig iPSCs allow for the production of chimeric animals that are partially composed of cells descended from one cell type and also composed of cells from a different cell type. Chimeric animals that are partially made from iPSCs allow for the study of how effectively iPSCs cause tumors and other iPSC issues. This is an essential study because chimeric mice that partially consist of iPSCs showed that iPSC derived chimeras possessed large numbers of tumors. This result raises significant concerns about the safety of iPSC therapies. Additionally, pig iPSCs can generate chimeras whose gametes are made from iPSCs. This can potentially revolutionize the transgenic animal field by enabling complex genetic manipulations (e.g. knockout or knockin of genes) to produce biomedically important large animal models or improve livestock production.

In this study, Steen Stice’s research group demonstrated the germline transmission of iPSCs with the live birth of a transgenic piglet that possessed genome integration of two human genes.  Additionally, gross and histological examination of necropsied porcine chimeras at 2, 7 and 9 months showed these animals lacked tumor formation and demonstrated normal development. The development of germline competent porcine iPSCs that do not produce tumors in young chimeric animals presents an attractive and powerful translational model to study the efficacy and safety of stem cell therapies and perhaps to efficiently produce complex transgenic animals.