Findings advance use of adult stem cells for replacement bone

Undergraduate is lead author of study in top national journal

In a significant advance for regenerative medicine, researchers at Rice University have discovered a new way to culture adult stem cells from bone marrow such that the cells themselves produce a growth matrix that is rich in important biochemical growth factors.
The research, which appears online this week in the Proceedings of the National Academy of Sciences, is notable not just because of the science – researchers found they could coax bone cells into produce up to 75 times more calcium – but also because the study was conducted by an undergraduate bioengineering senior, Néha Datta.

“These results are important, not just because they hold great promise for regenerating healthy bone but also because they may be applicable to other tissues,” said researcher Antonios Mikos, the John W. Cox Professor of Bioengineering and Director of Rice’s Center for Excellence in Tissue Engineering. “This is also a notable personal achievement for Néha, because PNAS is one of the top scientific journals in the country and because this is the third peer-reviewed paper – and the second first-authored paper — that she’s produced in the past year.”

Tissue engineering, also known as regenerative medicine, involves harvesting stem cells from a patient’s body and using them to grow new tissues that can be transplanted back into the patient without risk of rejection. Most tissue engineering approaches involve three components: the harvested adult stem cells, growth factors that cause the stem cells to differentiate into the right kind of tissue cells – like skin or bone – and a porous scaffold, or template, that allows the tissue to grow into the correct shape.

“Finding the right combination of growth factors is always a challenge,” Mikos said. “It’s not unusual for adult stem cells to progress through a half-dozen or more stages of differentiation on their way to becoming the right tissue – and any missed cue will derail the process. In most cases, engineers have little choice but to take a trial-and-error approach to designing a growth-factor regime.”

In the study, Mikos’s team hit upon the idea of having the stem cells create the proper growth medium themselves. The group, which included graduate student Quynh Pham and postdoctoral research associate Upma Sharma, accomplished this by seeding discs of titanium mesh with stem cells and encouraging them to form extracellular matrix, or ECM, the boney, calcified deposit that gives bone its structural strength.

A comparison was then run on these pre-generated ECM constructs and on non-treated titanium scaffolds. The pre-treated surfaces encouraged calcification at a much faster rate. The researchers also found up to 75 times more calcium in the bone created by tissues in the pre-treated cultures.

“To me, the most important element of the research is that it may one day contribute to new treatment options for patients,” said Datta, who is planning to enter medical school in the fall. “One of the reasons I want to become a surgeon is so I can help bring cutting-edge work from the laboratory into clinical practice.”

Datta said one of the main reasons she chose to attend Rice was because of the tremendous opportunities available through Rice’s Century Scholars Program. The program included funding for tuition as well as a chance to begin research in Mikos’s lab during her freshman year.

“My research experience at Rice has been life-changing in ways I could never have imagined four years ago,” Datta said. “I never anticipated I would be traveling to international conferences, for example, but from the very beginning Dr. Mikos treated me as a valuable member of his research team. He provided encouragement. He let me follow my ideas. In short, he is the perfect mentor.”