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.
Reference:
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
