Researchers from Johns Hopkins have discovered the presence of functional ion channels in human embryonic stem cells (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 appears 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," says Ronald A. Li, Ph.D., an assistant professor of medicine at The Johns Hopkins University 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," says Li. "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," says Li. "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," says Li. "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 adds that much more work is necessary to know for sure.
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The research was funded by the National Institutes of Health, the Blaustein Pain Research Center, the Croucher Foundation and the Hong Kong Research Grant Council.
Authors of the paper are Li, Tian Xue, Suk-Ying Tsang, Rika Van Huizen, Zhaohui Ye and Linzhao Cheng of Johns Hopkins; Kai Wang, Chun Wai Wong, Kevin W. Lai, Ka Wing Au, Janet Zhang, Gui-Rong Li, Chu-Pak Lau and Hung-Fat Tse of the University of Hong Kong.
