Todd Ransom of UC Riverside reports:
A new development in stem cell research has resulted from a completed study by a collaboration of scientists using the drug Rapamycin to inhibit mTOR, an intracellular protein necessary in cell proliferation. UCR’s Jiayu Liao, assistant professor in the Department of Bioengineering at Bourns College of Engineering, recently published a paper on the results in the Proceeding of the National Academy of Sciences dealing with human embryonic stem cell pluripotency.
His team inhibited mTOR using Rapamycin, a drug approved by the Food and Drug Administration, and found that pluripotency (the ability to create all cell types) was impaired, stem cell self-renew was prevented, and endodermal and mesodermal differentiation were enhanced.
“Stem cells can potentially develop into cancer,” Liao said. “That’s why it is important to be certain that any stem cells introduced into patients do not remain pluripotent, which has the potential to form tumors. The use of Rapamycin could potentially prevent this problem.”
Stem cells can differentiate into and of the three germ layers: the endoderm (interior stomach lining, gastrointestinal tract, the lungs), the mesoderm (muscle, bone, blood, urogenital), or the ectoderm (epidermal tissues and nervous system). Pluripotent stem cells can give rise to any fetal or adult cell type. However, alone they cannot develop into a fetal or adult animal because they lack the potential to contribute to extra embryonic tissue, such as the placenta.
“You don’t want to maintain pluropotency when using stem cells for treatment,” Liao said. “You want them all to differentiate into one of the three germ layers.”
The discovery could have a significant impact on the future use of stem cells in regenerative medicine, he added. Rapamycin itself is also an immunosuppressant which prevents rejection of organ transplantation from the host.
“It really opens the door for stem cell research towards translational medicine” he said.
In addition, because the drug is FDA approved, there is no need to order clinical trials for safety so the method can be placed into treatment immediately.
Here’s the abstract:
“Despite the recent identification of the transcriptional regulatory circuitry involving SOX2, NANOG, and OCT-4, the intracellular signaling networks that control pluripotency of human embryonic stem cells (hESCs) remain largely undefined. Here, we demonstrate an essential role for the serine/threonine protein kinase mammalian target of rapamycin (mTOR) in regulating hESC long-term undifferentiated growth. Inhibition of mTOR impairs pluripotency, prevents cell proliferation, and enhances mesoderm and endoderm activities in hESCs. At the molecular level, mTOR integrates signals from extrinsic pluripotency-supporting factors and represses the transcriptional activities of a subset of developmental and growth-inhibitory genes, as revealed by genome-wide microarray analyses. Repression of the developmental genes by mTOR is necessary for the maintenance of hESC pluripotency. These results uncover a novel signaling mechanism by which mTOR controls fate decisions in hESCs. Our findings may contribute to effective strategies for tissue repair and regeneration.”
Get the full text here (access required).
[Via UC Riverside PR]
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