Authors:
West FD, Terlouw SL, Kwon DJ, Mumaw JL, Dhara SK, Hasneen K, Dobrinsky JR, & Stice SL
Summary:
Ethical and moral issues rule out the use of human induced pluripotent stem cells (iPSC) in chimera studies that will determine the full extent of their reprogrammed state, instead relying on less rigorous assays such as teratoma formation and differentiated cell types. To date, only mouse iPSC lines are known to be truly pluripotent. However, initial mouse iPSC lines failed to form chimeric offspring, but did generate teratomas and differentiated embryoid bodies, and thus these specific iPSC lines were not completely reprogrammed nor truly pluripotent. Therefore there is a need to address whether the reprogramming factors and process used eventually to generate chimeric mice are universal and sufficient to generate reprogrammed iPSC that contribute to chimeric offspring in additional species. Here we show that porcine MSCs transduced with six human reprogramming factors (POU5F1, SOX2, NANOG, KLF4, LIN28 and C-MYC) injected into preimplantation stage embryos contributed to multiple tissue types spanning all 3 germ layers in 8 of 10 fetuses. The chimerisim rate was high, 85.3% or 29 of 34 live offspring were chimeras, based on skin and tail biopsies harvested from 2 to 5 day old pigs. The creation of pluripotent porcine iPSCs capable of generating chimeric offspring introduces numerous opportunities to study the facets significantly affecting cell therapies, genetic engineering and other aspects of stem cell and developmental biology.
Source:
Stem Cells & Development; (04/09/10)