Naïve Human Stem Cells to Promote Research in Regenerative Medicine and Human Development

Discovery of a method for maintaining human induced pluripotent stem cells (iPS cells) in their earliest, most primitive, naïve state is expected to promote research into their use in regenerative medicine, patient-specific iPS cell disease modeling, and the study of early human development in vitro and in vivo.

Induced pluripotent stem cells are usually created by inserting four genes into the genomes of such adult cells as skin cells and then culturing the modified cells with a cocktail of growth factors. The differentiated cells then revert to an embryonic-stem-cell-like state from which they can mature into a multitude of different cell types. The problem has been the lack of a method to hold the stem cells in the undifferentiated state for any length of time.

Investigators at the Weizmann Institute of Science (Rehovot, Israel) worked on this problem with both mouse and human cells. In particular, they were interested in establishing a technique to preserve human iPS cells in their earliest, naïve state that would mimic the behavior of mouse stem cells, which naturally remain in an undifferentiated state for much longer.

They reported in the October 30, 2013, online edition of the journal Nature that they had successfully established defined conditions that facilitated the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human embryonic stem cells, from somatic cells through iPS cell reprogramming, or directly from blastocysts. The novel naïve pluripotent cells retained molecular characteristics and functional properties that were highly similar to mouse naive embryonic stem cells, and distinct from conventional primed human pluripotent cells.

"These cells correspond to the earliest stages of human embryonic stem cells that have been isolated. We managed to freeze what is essentially a very fleeting situation and to produce a new, naïve, pluripotent state in stem cells," said senior author Dr. Jacob H. Hanna, professor of medical genetics at the Weizmann Institute of Science. "When we grow the cells in the petri dish we do not know if they are maintaining their original state as in the embryo. This is what is new: this is the first time that we can keep the cells in what we call the naïve configuration. The challenge for us now is how to take these naïve cells and in the petri dish make a liver, or, from our study, it starts creating the possibility that with these cells you may consider growing organs in other species. We do not know if that works. There are a lot of ethical issues to consider. But we have put this on the table."

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Weizmann Institute of Science