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Porcine IPSC Therapy Model System

The promise of stem cell therapies to help treat and maybe one day cure diseases such as Parkinson’s, Alzheimer’s, Huntington’s , Diabetes and many others has been the long term dream of researcher with daily advances bring us closer and closer. Stem cell treatments for many diseases have been developed in the mouse. However questions remain whether these cell therapies will be able to be translated from the mouse to human patients. It has become clear in many fields that a large animal model more similar to humans is needed as an intermediate step to transition these therapies from mouse to humans. The pig is a desirable large animal model that has similar anatomy and physiology to humans and has been an important model for diabetes, atherosclerosis and traumatic brain injury. However, porcine stem cells derived from the inner cell mass of developing blastocysts have proven to have limited pluripotency. These cells typically possess embryonic stem cell (ESC) like morphology and express a limited number of markers, yet fail more stringent pluripotency tests such as contribution to chimeric animals. This has made it impossible to study same species stem cell therapies in the pig. Our lab has recently developed porcine induced pluripotent stem cells (piPSCs) by overexpressing the human POU5F1, SOX2, NANOG, LIN28, KLF4 and C-MYC genes. piPSCs showed ESC morphology, immunoreactivity and for the first time contribution to tissues representing all 3 germ layers and potently the germline in chimeric offspring. These cells can now be differentiated into multiple lineages including endothelial cells, mesencymal cells and neural cells for use in cell therapy and tissue engineering applications.

Pig induced pluripotent stem cells express the pluripotency markers SSEA4 (left) and TRA 1-81 (right).

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