Researchers have developed a new method of detecting chemicals that are secreted as stem cells differentiate into osteocytes, allowing scientists to study the complex bone stem cell differentiation process.
Mesenchymal stem cells go through a complex process before maturing into osteocytes. Mesenchymal stem cells transform into osteoblast progenitor cells, then pre-osteoblasts, and osteoblasts before maturing into osteocytes. A variety of different molecules are involved in the differentiation process such as osteopontin, collagen type I, osteonectin, osteocalcin, and Bone Morphogenic Protein 2 (BMP-2). The concentrations of these molecules could potentially be used to monitor the differentiation process as the concentration of the molecules changes throughout differentiation. Unfortunately, current methods of detecting these molecules are not sensitive enough to allow any one of those molecules to serve as a suitable biomarker for monitoring stem cell differentiation in real time.
An international team of researchers from the University of Cambridge, University of Bologna, and Mines Saint-Etienne have made a breakthrough and have developed a new technique that allows the differentiation process to be detected in real time using an organic electrochemical transistor (OECT) with a gate electrode that is sensitive to one of the molecules involved in the differentiation process – BMP-2.
The OECT is a device consisting of a three-terminal transistor with a source, drain, and gate, along with a connecting channel made of a PEDOT-PSS conducting polymer. On the gate, the researchers anchored antibodies that bind to BMP-2. When BMP-2 binds to the antibodies, the current running through the OECT changes and is detectable. The change in current indicates the level of BMP-2. The researchers say the OECT is sufficiently sensitive to be capable of detecting BMP-2 at the levels required to induce stem cell differentiation in vitro.
The researchers suggest that their OECT could potentially detect other important cytokines involved in the stem cell differentiation process or analytes such as osteopontin, osteonectin, or osteocalcin by making changes to the gate electrode and using different antibodies.
While the OECT should allow the stem cell differentiation process to be studied, the system could be adapted and used for studying the early stages of disease by adding antibodies that bind to a range of different biomarkers present in body fluids. It may also be possible to incorporate the OECT into novel smart bandages which could detect biomarkers of infections.
The researchers are currently engaged in a project with the European Space Agency to study the differentiation of bone stem cells in astronauts> Their system could help to detect and prevent bone and muscle fragility in long term space missions. The in vitro pre-screening models they are developing could also be of benefit for developing stem cell therapies for bone disorders such as brittle bone disease and osteoporosis.
The new technique is detailed in the paper – BMP-2 functionalized PEDOT:PSS-based OECTs for stem cell osteogenic differentiation monitoring – which was recently published in Flexible and Printed Electronics. DOI: 10.1088/2058-8585/ab5bfc