Porcine pluripotent stem cells and their differentiation

Abstract

In some situations, the pig has advantages over the mouse as a model in biomedical research. The availability of pluripotent cell lines is likely to broaden this appeal. Here we review progress in the derivation and characterization of embryonic stem cells (ESC) and induced pluripotent lines (iPSC) from pigs. Until recently, most porcine ESC failed to meet the full criteria for pluripotency, but that may be changing as more becomes known about the culture conditions required to maintain epiblast outgrowths from early porcine conceptuses in an undifferentiated, self-renewing state. In addition, porcine iPSC cells have been generated, some with the features of FGF2-dependent epiblast-type cells, typified by human ESC, and others that require LIF and resemble the “ground state”, na ï ve-type mouse ESC. Despite these successes, incomplete reprogramming and loss of pluripotency when selection conditions are relaxed continue to be problems that must be overcome if the full potential of iPSC is to be realized. The most immediate value of iPSC may relate to their ability to proliferate almost indefinitely in culture, thus enabling more complex genetic manipulations of the genome through growth selection than could be performed in other cell types. The “undifferentiated” state of iPSC may also allow improved cloning efficiency, although this remains to be proved. Finally, the pig will likely prove useful in testing stem cell-based therapies, although only a limited number of experiments demonstrating that the porcine iPSC can be directed to transform into more specialized sub-lineages and then form functional grafts have been performed.