Stanford doctors advance in bid to turn mice stem cells into blood vessels

Starting with embryonic stem cells derived from mice, surgical resident Oscar Abilez, MD, and colleagues have successfully differentiated the stem cells into myocytes, one of the building blocks of blood vessels, after placing them in a life-like growth environment that the research team had created. The scientists hope to be able to eventually grow whole blood vessels that can be transplanted back into mice.

The work is being performed in the laboratory of Christopher Zarins, MD, professor of surgery.

“It's very odd,” Abilez said. “We get these stem cells and grow them into contracting myocytes in cultures: You really see them contracting, you really know they're alive, and you start to believe this stem cell stuff has possibilities.”

For the study, Abilez received first place in the seventh annual International Society of Endovascular Fellows' research award in laboratory sciences. The findings are published in this month's edition of the Journal of Endovascular Therapy.

The ultimate goal of the research is to bring together two of today's most promising areas of medical investigation: stem cell research and tissue engineering. Tissue engineering, the growth of organs and tissues outside the body for replacement, has achieved successful transplantations of a variety of human tissues including skin and corneas. Most recently, a team of researchers at Wake Forest University in Winston-Salem, N.C., performed the successful transplantation of laboratory-grown bladders into seven children.

Tissue-engineered blood vessels have also seen some success when transplanted into animal models, but still face a variety of limitations, Abilez said, key among them rejection by the immune system. By creating a tissue-engineered blood vessel grown from a patient's own stem cells, this rejection could potentially be eliminated, Abilez said.

“Our goal is to derive all the different cell types from the same, original cell,” Abilez explained. “This would be new for an engineered tissue. We hope our work with mouse stem cells could eventually be translated to human autologous adult stem cells.”

With an estimated 70 million Americans diagnosed with cardiovascular disease, the need for arterial vascular grafts continues to grow. In 2002, there were 1.5 million medical procedures done that required replacement blood vessels.

“This is an exciting, emerging research front,” said John Cook, MD, PhD, professor of medicine (cardiovascular medicine). “It has great potential for therapeutic applications.”

Abilez's success is due in part to a custom-made bioreactor that researchers built in their laboratory; it has the capability of delivering controlled chemical, electrical and mechanical stimulation to the stem cells. Bioreactors have been used for centuries as fermentation chambers for growing organisms such as bacteria and yeast, but only recently have they been used in stem cell research labs.

“Oscar is the first one to really create an environment which cells see in real life,” Zarins said. “He's the first one to really create the multiplicity of biomechanical stresses and strains that the vascular system experiences in everyday life when you simply get up and walk around the block.” The computer-controlled bioreactor was developed to help create a standardized process for differentiating stem cells in laboratories that could be used around the world.

“The idea behind it is that you can control various conditions to try to make these stem cells become the cells you want,” Abilez said. “Our goal is to take the mouse stem cells and find the conditions that will make the stem cells into smooth muscle cells (myocytes), endothelial cells and fibroblasts, which make up the three layers of a blood vessel. The idea is if we can optimize our yield we can more easily obtain the large number of specific cells required to make a blood vessel.”