By: 5 October 2016
US researchers use a single molecule to command stem cells to build new bone

Researchers at the University of California San Diego have discovered an easy and efficient way to coax human pluripotent stem cells to regenerate bone tissue – by feeding them adenosine, a naturally occurring molecule in the body.

The stem-cell-derived bone tissue helped repair cranial bone defects in mice without developing tumours or causing infection.

The work could lead to regenerative treatments for patients with critical bone defects and soldiers who have suffered traumatic bone injuries. The findings, published in Science Advances, could also lead to a simple, scalable and inexpensive way to manufacture a pure population of bone-building cells.

“One of the broader goals of our research is to make regenerative treatments more accessible and clinically relevant by developing easy, efficient and cost-effective ways to engineer human cells and tissues,” said Shyni Varghese, a bioengineering professor at UC San Diego and senior author of the study.

Pluripotent stem cells are capable of differentiating to become any type of cell in the body, such as muscle, heart, skin or bone, and have promising therapeutic uses to repair or regenerate various tissues and organs. But directing stem cell differentiation is like following a complex recipe, involving a long list of ingredients and steps that make the process costly and inefficient. Another challenge is producing stem-cell-derived tissues or organs that don’t develop teratomas when transplanted.

Varghese and her team showed that they could control the differentiation of human pluripotent stem cells into functional osteoblasts simply by adding adenosine to their growth medium. Like living bone cells in the body, the resulting osteoblasts built bone tissues with blood vessels. When transplanted into mice with bone defects, the osteoblasts formed new bone tissues in vivo without any signs of teratoma formation.

Varghese’s team is now investigating exactly how adenosine signalling promotes bone formation. So far, they’ve attributed the signalling to a receptor on the stem cells’ surface, called the A2bR receptor, which binds to adenosine. But this mechanism still requires further study, she said.

Source: University of California


Reference: Kang, H., Shih, Y.-R.V., Nakasaki, M., et al. Small molecule-driven direct conversion of human pluripotent stem cells into functional osteoblasts. Science Advances. DOI: 10.1126/sciadv.1600691.