Induced Pluripotent Stem Cell Lines Derived From Human Somatic Cells

Abstract

Because the mammalian embryo is regulated by epigenetic rather than genetic events, differentiation is—in principle—reversible. Somatic cell nuclear transfer permits trans-acting factors resident in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. The investigators have found that 4 genes (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that possess the defining features of embryonic stem (ES) cells. Each of 4 induced pluripotent stem (iPS) cells had the typical human ES cell morphology and a normal karyotype after up to 17 months of culture. Each iPS clone expressed telomerase activity and human ES cell-specific cell surface antigens. All of the reprogrammed iPS clones were able to give rise to differentiated derivatives of all 3 primary germ layers. When human newborn foreskin fibroblasts were transduced, each clone consisted of cells having a human ES cell morphology and genes characteristic of human ES cells. When last examined after 14 weeks, all of the iPS clones were proliferating vigorously. Each clone exhibited multilineage differentiation in both embryoid bodies and teratomas. Except for the fact that human iPS cells are not derived from embryos, they meet defining criteria for human ES cells. They should prove helpful when studying the development and function of human tissues. Once technical limitations such as mutation through viral integration are effectively addressed, the cells should find use in transplantation treatments. With the exception of autoimmune diseases, patient-specific iPS cell lines should mostly eliminate concern over immune rejection.