Investigators at the Trinity Centre for Bioengineering (TCBE) are exploring the use of adult Mesenchymal Stem Cells (MSCs) for orthopaedic therapies. MSCs are defined as multipotent cells capable of differentiating into various cell types such as osteoblasts, chondrocytes, adipocytes and others. MSCs are also known secrete biologically active molecules that exert beneficial effects on other cells and tissues. Such MSC paracrine effects can be divided into trophic, immunomodulatory, anti-scarring and chemo-attractant. Therefore MSCs are being investigated clinically both as building blocks for the development of new tissue, by controlling their differentiation into specific cell types, and for their paracrine effects. Tissue engineering strategies involving MSCs, scaffolds and bioactive factors to regenerate functional tissue has emerged as a promising therapy in orthopaedics.
There exists significant expertise in the TCBE in all three aspects of this ‘tissue engineering triad’ – stem cell biology, biomaterial scaffolds and both physical and biological signals. A central focus of the TCBE is to understand how extrinsic signals regulate MSC differentiation, with the objective of harnessing this knowledge to promote tissue specific differentiation for such regenerative purposes. Specifically, significant experience exists in the development of scaffolds to provide the appropriate structural and biological signals to guide MSC differentiation. Furthermore, we have developed novel bioreactor systems to control the physical environment of cells, which has been shown to not only to regulate the phenotype of MSCs, but also the quality of the tissues they produce.
A number of grand challenges exist in this field which are currently being addressed by researchers at the TCBE. These include the identification of an appropriate source of MSCs for a particular therapeutic application, a means to isolate and expand these cells without loss of function, and critically the means to control the phenotype of MSCs once implanted into a damaged or diseased environment. This can potentially involve the manipulation of MSCs in vitro, or alternatively through the development of novel implants that incorporate minimally manipulated MSCs and/or recruit local progenitor cells to a damaged tissue, and subsequently controlling their activity by modulating the physical and biological signals they experience.
Novel projects in these area in the TCBE include – the development of growth factor or gene delivery scaffolds, the exploration of the therapeutic potential of MSCs isolated from diseased joints and the development of in vitro culture systems that enable the engineering of tissues using MSCS with compositions and organizations mimicking that of normal tissue. These projects are being conducted with clinical collaborators to facilitate rapid translation to the clinic. While the initial focus has been in the field of orthopaedics, there exists a clear potential to expand this expertise into other areas of medicine.