“By simply changing the glucose levels we were able to control whether the cells tended toward stem cells or remained in a mature state,” said Clifford Folmes, Ph.D., lead investigator of the Mayo Clinic study, which appears in the August 3 edition of the journal Cell Metabolism.
To show how sugar and metabolism affect so-called “cell fate,” Mayo Clinic investigators genetically reprogrammed an ordinary cell type, called a fibroblast, to become induced pluripotent stem cells (iPS cells), an embryonic-like cell with the potential to become just about any type of tissue in the human body.
“We’re advancing the next chapter in understanding the building blocks of regenerative medicine,” says Andre Terzic, M.D., Ph.D., head of Mayo’s Center for Regenerative Medicine and senior author of the study. “Unraveling one further mystery in the process will accelerate translation from principles to practice.”
Stem cells form the building blocks of regenerative medicine, and iPS cells represent a promising avenue of research for many reasons.
Embryonic stem cells, which are the product of in vitro fertilization, have similar therapeutic potential but are mired in ethical and legal issues. Adult stem cells, present in bone marrow and blood, for instance, and perinatal stem cells, harvested from umbilical cord, have more limited potential for becoming new tissue types.
Researchers around the world, therefore, are focused on iPS cells as a regenerative source for a range of organs damaged by disease.
This new branch of medicine could someday help treat a range of cancers, like multiple myeloma, lymphoma and leukemia, and autoimmune disorders. It also may some day help patients grow new cardiac tissue for a heart damaged during heart attack, brain cells damaged by stroke or pancreatic islet cells lost to diabetes, to name just a few.
Scientists recognize the iPS cell potential for regeneration, but they don’t completely understand the underlying requirements. Findings from this study will bolster that basic scientific foundation while improving researchers’ ability to grow iPS cells for diverse applications.
To help shed light on iPS cell derivation, Dr. Folmes and colleagues used magnetic resonance spectroscopy and a battery of high-throughput technology. The research team discovered that nuclear reprogramming converts a cell’s basic metabolic function (bioenergetics) away from oxygen-dependent aerobics (somatic oxidative metabolism) and instead favors sugar utilization by anaerobics (glycolytic flux).
Other members of the research team included: Timothy Nelson, M.D., Ph.D.; Almudena Martinez-Fernandez, Ph.D.; D. Kent Arrell, Ph.D.; Jelena Zlatkovic Lindor, Ph.D.; Petras Dzeja, Ph.D.; Yasuhiro Ikeda, D.V.M., Ph.D.; and Carmen Perez-Terzic, M.D., Ph.D., all of Mayo Clinic.
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