Beating heart cells (cardiomyocytes) are often used as an empowering imagery to depict important scientific advances in stem cell technology; advances that enable scientists to harness human embryonic stem cells to regenerate tissues that cannot easily be replaced, including heart tissue. From the use of controversial human embryonic stem cells, to Yamanaka's discovery of an engineering technology to reprogram human skin cells into cells that are akin to embryonic stem cells (dubbed induced pluripotent stem cells); the beating cardiomyocytes remain a media cliché representing our society's advances in stem cell technology and regenerative medicine.
That being said, the origin of the beating cardiomyocytes in a video released by UCSF (below) may actually surprise you. Departing from the usual suspects, these cardiomyocytes are derived from a rare population of stem cells collected from human breast tissue donated by healthy adult subjects; a population dubbed endogenous "pluripotent" stem cells (ePSCs). Recently discovered by Dr. Thea Tlsty, a renowned breast cancer biologist at UCSF, ePSCs are so named because of their "pluripotency": which simply defines the cell's capacity to give rise to any component of the embryo, in manner much like embryonic stem cells.
In the recent March 2013 publication in the Proceedings of the National Academy of Sciences, Tlsty reported the discovery of ePSCs in a population of primary human breast cells expressing low levels of p16ink4a (a tumor suppressor gene involved in controlling cell division and suppressing cancer). ePSCs express molecular signatures of embryonic stem cells, and possess the capacity to regenerate any human tissue, much like human embryonic stem cells. Interestingly, ePSCs differ from embryonic stem cells in that they are mortal; supporting only 60 cell divisions, and the production of over 1 billion daughter cells.
According to Tlsty's data, ePSCs are not derived from adult stem cells in the breast tissue ( a.k.a. mammary stem cells); stem cells that can regenerate only the cellular components that make up the breast tissue. While mammary stem cells can sometimes undergo changes that can enable them to differentiate into heart cells; Tlsty found that despite these changes, mammary stem cells still differed significantly from ePSCs in their molecular properties and behavior. This suggests that ePSCs are not the product of mammary stem cells, but are rather a distinct stem cell population in the adult tissue that retains the pluripotent properties of embryonic stem cells.
Tlsty's discovery of ePSCs begs the question as to whether this adult source of pluripotent stem cells can be safely used for regenerative medicine. According to Dr. Tlsty, the answer is a resounding yes. "Unlike immortal embryonic stem cells, or [Yamanaka's] induced pluripotent stem cells, that demonstrate a high degree of genetic instability," says Tlsty, "ePSCs are mortal and genetically stable." Because genetic instability often gives rise to molecular aberrations contributing to cancer, the fact that ePSCs are genetically stable suggests that they are very unlikely to cause cancer, and are therefore a much safer alternative to embryonic or reprogrammed sources of pluripotent stem cells. Tlsty further assured that it is perfectly normal for ePSCs to express low levels of the tumor suppressor gene, p16ink4a. "[Indeed], low p16ink4a expression is often seen in non-cancerous cells in normal conditions," according to Tlsty, "High levels of p16ink4a expression occur only when cells are stressed."
Overall, Tlsty’s remarkable data suggest that ePSCs represent a natural repair kit in adult tissues that can safely regenerate any tissue in the body- a key discovery that will change the way people think about the regenerative capacity of adult tissue. An interesting challenge may be to figure out how to effectively tap into this rare source of "pluripotent" stem cells in adult tissue; a potential breakthrough that might one day replace the need for highly controversial embryonic stem cells, or Yamanaka's induced pluripotent stem cells in which molecular flaws are still a concern.
Roya, S., Gascarda, P., Dumonta, N., Zhao, J., Pana, D., Petriea, S., Margetab, M. Tlsty, T.D. Rare somatic cells from human breast tissue exhibit extensive lineage plasticity. PNAS, March 2013 www.pnas.org/cgi/doi/10.1073/pnas.1218682110