Researchers from Johns Hopkins have discovered the
presence of functional ion channels in human embryonic stem
cells, or ESCs. These ion channels act like electrical
wires and permit ESCs, versatile cells that possess the
unique ability to become all cell types of the body, to
conduct and pass along electric currents.
If researchers could selectively block some of these
channels in implanted cells, derived from stem cells, they
may be able to prevent potential tumor development. The
paper appeared Aug. 5 online in the journal Stem
Cells.
"A major concern for human ESC-based therapies is the
potential for engineered grafts to go haywire after
transplantation and form tumors, for instance, due to
contamination by only a few undifferentiated human ESCs,"
said Ronald A. Li, an assistant professor of
medicine at the School of Medicine and senior author of
the study. "Our discovery of functional ion channels, which
are valves in a cell's outer membrane allowing the passage
of charged atoms, the basis of electricity, provides an
important link to the differentiation, or maturation, and
cell proliferation, or growth, of human ESCs."
Because human ESCs can potentially provide an
unlimited supply of even highly specialized cells, such as
brain and heart cells, for transplantation and cell-based
therapies, they may provide an ultimate solution to limited
donor availability.
In an earlier study, Li's lab genetically engineered
heart cells derived from human ESCs, suggesting the
possibility of transplanting unlimited supplies of healthy,
specialized cells into damaged organs.
"We do not want to be taking any chances of tumor
formation. Based on our previous research, we therefore
decided to explore the existence of ion channels in
pluripotent, or versatile, human ESCs because electrical
activity is known to regulate cell differentiation and
proliferation," Li said. "To my knowledge, the electrical
properties of human ESCs were never studied up to this
point."
In the current study, the researchers measured the
electric currents of single human ESCs, discovered several
channels that allow and control passage of potassium and
observed the electric current's effect on cell
differentiation and proliferation.
"In a number of different cell types, from cancer to
T-lymphocytes, potassium channels are responsible for
altering the membrane voltage of cells," Li said. "This in
turn is required for the progression of certain cells into
the next phase of a cell cycle."
Li hopes the targeting of specific potassium channels
will give scientists more understanding and control in
engineering healthy cells for transplantation.
"We found that blocking potassium channels in ESCs
also slowed their growth," Li said. "Our findings may lead
to genetic strategies that suppress undesirable cell
division after transplantation, not only for ESCs and their
derivatives but perhaps for adult stem cells as well." Li
added that much more work is necessary to know for sure.
The research was funded by the National Institutes of
Health, Blaustein Pain Research Center, Croucher Foundation
and Hong Kong Research Grant Council.
Authors of the paper are Li, Tian Xue, Suk-Ying Tsang,
Rika Van Huizen, Zhaohui Ye and Linzhao Cheng, all of Johns
Hopkins; and Kai Wang, Chun Wai Wong, Kevin W. Lai, Ka Wing
Au, Janet Zhang, Gui-Rong Li, Chu-Pak Lau and Hung-Fat Tse,
all of the University of Hong Kong.