Chemists from New York and Glasgow have discovered the molecules that guide stem cells to differentiate into particular types of cells. One of the researchers, Rein Ulijn, Ph.D. of the City University of New York and the University of Strathclyde, produced gels that mimic bone’s stiffness, thus causing stem cells placed on the gel to differentiate (alter its shape or properties). The study was published on July 27, 2016 in the journal Chem.
“This paper is a great example of how chemistry can help make step changes in biology, ” says Matthew Dalby, Ph.D., a professor of cell engineering at the University of Glasgow and co-senior author on the study with Dr. Ulijn, in the July 27, 2016 news release. “As a biologist, I needed simple yet tunable cell-culture gels that would give me a defined system to study metabolites in the laboratory. Rein had developed the chemistry to allow this to happen.”
“Although transcription factors are often the ingredients scientists use to induce stem cell fate, Dalby and Ulijn hypothesize that certain metabolites ‘fuel’ the pathways that result in variable concentrations of transcription factors that drive these changes. One metabolite featured in the study is cholesterol sulfate, which was found to be used up during osteogenesis on a rigid matrix and in turn could be used to convert stem cells into bone-like cells in a dish. In the paper, the researchers illustrate how it could influence proteins that activate the transcription factors that transcribe major bone-related genes to drive bone formation—showing a link between metabolite usage and activation of transcription factors.”
Dr. Dalby told OTW, “A range of stem cell directing bioactive materials are under development that could be injected into non-union sites, osteoporotic fractures, areas in need of grafting to scaffold autologous stem cell therapies and to direct the stem cells in situ without the need for drugs.”
“We are hoping to discover alternative drugs. Many surgeons are aware of the benefits but also the potential problems of BMP2 use in bone therapies. Identification of bioactive metabolites may provide safer alternatives with fewer systemic side effects. The future lies in (1) improved gel formulations to allow progress through to FDA approval and (2) in vivo testing of metabolite drugs to allow clinical trials to commence.”
