US researchers have been awarded a four-year, $2.6 million grant from the National Institutes of Health to research into the development of ‘bone spackle,’ an engineered tissue that may one day be used to help bone injuries heal faster and stronger.
George Plopper, an assistant professor of biology at Rensselaer Polytechnic Institute, and graduate students Roman Salasznyk and Rob Klees work with adult human mesenchymal stem cells (hMSC) that have the specialised potential to become one of three forms of connective tissue – bone, cartilage, or fat. These adult stem cells are extracted from banked bone marrow samples and then grown in the Rensselaer biology lab.
Chemicals are often used in culture dishes to artificially stimulate hMSC to differentiate into bone. In the body, however, these chemicals can cause a number of problems including liver toxicity, immune system disorders, and infection.
Plopper’s goal is to develop bone reliably from stem cells without the use of chemicals. The researchers have selected a specific protein, called focal adhesion kinase (FAK), a decision-making protein that may signal stem cells to become bone at an early stage of differentiation. The researchers hope that ‘turning on’ FAK will be a chemical-free method of creating engineered bone cells that could be safely used in people who eventually receive such treatment.
The researchers also want to learn to recognise when stem cells begin the transformation to bone, as opposed to turning into cartilage or fat. ‘Markers already exist for fully differentiated mature bone cells,’ said Plopper, ‘but it is more difficult to discern the point where stem cells begin to change in the direction of becoming bone.’
Kristin Bennett, an associate professor of mathematical sciences at Rensselaer, is providing the predictive analysis equations that ultimately will sort out the set of conditions that will cause the hMSC to differentiate into bone cells.
Also on the team is consultant Deepak Vashishth, assistant professor of biomedical engineering at Rensselaer, and Adele Boskey, professor of biochemical and cellular and molecular biology and director of research at the Hospital for Special Surgery in New York.
Someday, these engineered bone cells could be directly injected into the site of a bone injury. Or, in the form of a paste, the cells could serve as a bone ‘spackle’ spread onto the ends of fractured bones, or used to fill in a crack.
Similar to a skin graft, applying this veritable jumpstart of bone cells would mean that ‘healing time should decrease significantly,’ said Plopper. ‘And that would mean patients wouldn’t have to wear casts for as long as they do now.’