A New Way To Screen Safe Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSCs) are derived from adult cells. Genetic engineering techniques that place specific transcription factors into adult cells turn on genes necessary for early development and turn off genes required for terminal differentiation. This reverts the adult cells to a more incipient state, and the become similar to embryonic stem cells.

Because iPSCs can be made from a patient’s own adult cells, they do not have as great a chance of being rejected by the patient’s immune system. Unfortunately, iPSCs show a robust ability to form tumors when transplanted into mice. The ability of iPSCs to cause tumors varies greatly from cell line to cell line and even individual cells within a particular iPSCs cell line vary in their ability to cause tumors. Some iPSCs show a tumorigenicity that exceeds that of embryonic stem cells, but others do not. Is there a way to screen for those cells that are prone to cause tumors and weed them out?

The laboratory of Timothy Nelson at Mayo Clinic in Rochester, MN has devised an ingenious technique that does exactly that. Alyson Smith and colleagues in Nelson’s laboratory used a cancer drug that destroys cancer cells that have acquired so many mutations that they can no longer effectively repair their DNA. Such drugs destroy cells that lack robust DNA repair, and tumor-causing iPSCs have exactly this problem. Thus treatment of the iPSC, with the drug etoposide purges the culture all of the rogue cells and generated and iPSC culture that no longer effectively forms tumors when transplanted into laboratory animals.

This technique does not affect the ability of the iPSC culture to differentiate into various cell types, but it does eliminate the cancer-causing cells and, therefore, the risk of using such a cell line for therapeutic purposes. This is a remarkable find that promises to revolutionized regenerative medicine.

See Alyson J. Smith, et al., Apoptotic Susceptibility to DNA Damage of Pluripotent Stem Cells Facilitates Pharmacologic Purging of Teratoma Risk. Stem Cells Trans Med 2012 vol. 1 no. 10 709-718.