The potential for enabling the differentiation of stem cells holds tremendous implications in organ growth and regeneration. “Repairing or replacing damaged organs requires proper direction of vessel growth to support organ function and we now know that sugars play a key role determining this direction,” said Dirk Hentschel, MD, of the Renal Division at BWH.
Differing from previous studies that focused on the role of growth factors in controlling differentiation, BWH researchers investigated the role sugars play. “Finding a way to control differentiation with sugars has the crucial advantage of reducing oncogenic risks associated with growth factor therapy in clinical settings,” said Rania Harfouche, PhD, research fellow in the Renal Division at BWH.
Using sugar sequencing techniques, researchers discovered that as embryonic stem cells differentiate into endothelial cells, the sugars on the cell surface change in composition to become more sulfated. Inhibiting this process prevents the formation of blood vessels. By knocking down the enzyme responsible for sulfation of sugars in a developing zebrafish embryo, the researchers observed abnormal vascular development that could be recovered using defined sulfated sugars. “This is a simpler solution to differentiation, compared to determining the exact combination of growth factors that a cell requires,” explains Shiladitya Sengupta, PhD of the Department of Medicine at BWH.
“The next step in this research is to determine specific sugar sequences that can promote efficient differentiation of stem cells into endothelium,” said Stephanie Piecewicz, a graduate student at MIT. The researchers believe that by providing the appropriate extracellular ‘net,’ the cell can capture the appropriate combination of physiological molecules that it needs to proceed through differentiation.
The Department of Defense and the American Heart Association funded this research.
About Brigham and Women’s Hospital:-
Brigham and Women’s Hospital (BWH) is a 777-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. In July of 2008, the hospital opened the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 860 physician-investigators and renowned biomedical scientists and faculty supported by more than $416 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses’ and Physicians’ Health Studies and the Women’s Health Initiative.
For more information about BWH, please visit http://www.brighamandwomens.org/