Monday, 6 January 2014

Biomaterials encourage stem cells to become bone-building cells

Shyni Varghese
With the help of biomimetic matrixes, a team of researchers led by bioengineers at the University of California, San Diego has discovered how calcium phosphate coaxes stem cells to become bone-building cells.

UC San Diego Jacobs School of Engineering professor Shyni Varghese and her colleagues have traced a surprising pathway from these biomaterials to bone formation. They believe that these findings will help them refine the design of biomaterials that encourage stem cells to give rise to new bone.

The researchers say the study may also point out new targets for treating bone defects and bone metabolic disorders such as major fractures and osteoporosis.

The materials are built to mimic the body's own cellular niches, in which undifferentiated or "blank-slate" stem cells from bone marrow transform into specific bone-forming cells. 

"We knew for years that calcium phosphate-based materials promote osteogenic differentiation of stem cells, but none of us knew why. As engineers, we want to build something that is reproducible and consistent,so we need to know how building factors contribute to this end." said Varghese.

The researchers found that when phosphate ions gradually dissolve from these materials, they are taken up by the stem cells and used for the production of ATP, a key metabolic molecule. An ATP metabolic product called adenosine then signals the stem cells to commit to becoming bone-forming cells.

Varghese said it was a surprise to her team that "the biomaterials were connected to metabolic pathways. And we didn't know how these metabolic pathways could influence stem cells' commitment to bone formation."

While the PNAS findings only apply to bone building, Varghese and her students at UC San Diego are working on a variety of projects to understand how stem cells thrive and differentiate into a variety of cell types. With this information, they hope to design biomaterials that can be used to help transform stem cells into tissues that may someday replace diseased or degenerated bone, muscle, or blood vessels.

Stem cell research may seem like an unusual endeavor for engineers, but tissue construction and the development of biomaterials have become one more type of "building" in the engineering repertoire, Varghese said.

"But to me, what we do is use engineering principles to solve a biological problem, and by integrating many research disciplines from molecular biology to engineering to medicine. This research is a testimony to how international collaborations could provide unique opportunities to young researchers to tackle interdisciplinary questions relevant to medical sciences." she added.

Image: Three human mesenchymal stem cells. The ATP in the cells is glowing green. The phosphate from the biomaterial (calcium phosphate) that is taken up by the cells is used to make more ATP, which is traditionally the source of energy for the cells. In this case, however, ATP can be converted to adenosine which promotes the human mesenchymal stem cells to be turned into bone cells. 

- Yu-Ru V. Shiha, YongSung Hwanga, Ameya Phadkea, Heemin Kanga, Nathaniel S. Hwange, Eduardo J. Caro, Steven Nguyen, Michael Siua, Emmanuel A. Theodorakis, Nathan C. Gianneschif, Kenneth S. Vecchio, Shu Chien, Oscar K. Lee, Shyni Varghese (2013). Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling PNAS : 10.1073/pnas.1321717111

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