Bone stem cells
Research in to the biology of bone stem cells in the Bellantuono group involves the use of Marrow-Derived Stem Cells (SC) – both hematopoietic (HSC) and mesenchymal (MSC), and their potential use in gene and cell therapeutics. The long-term aim is to use stem cells:
- to correct disorders of bone such as rheumatoid arthritis or inherited disorders of the skeleton.
- to enhance HSC engraftment post-transplantation, especially when HSC numbers are small such as in cord blood transplantation in adults.
MSC are non-hematopoietic progenitor cells originally isolated from bone marrow, capable of differentiating into tissues such as bone and cartilage. Several groups including our own have shown that they can be readily isolated by plastic adherence, expanded several fold and genetically modified by viral vectors. Furthermore, they can support the survival and proliferation of human HSC.
Thus, clinically they are good candidates to correct bone diseases and to improve HSC transplantation. Crucial to the success of any of these strategies is efficient migration and long-term engraftment to those tissues. So far, results have shown that although MSC can engraft to those tissues, levels are at the limit of detection and engraftment is transient. Higher and persistent levels are required to achieve a therapeutic benefit in the majority of applications. We believe that two main problems are responsible for the lack of MSC engraftment – ageing of MSC during ex vivo expansion and reduced migration capacity to bone marrow.
Right: Human embryonic derived mesenchymal progenitor cells (hES-MP) growing on a polyurethane scaffold nuclei are stained blue and the cytoskeleton is in red.
Parallel work in the Reilly group uses adult bone marrow derived and embryonic derived mesenchymal stem cells to grow bone matrix for repair of orthopaedic defects. We are particularly interested in mechanical cues that trigger mesenchymal stem cell differentiation as well as chemical and physical cues that come from the cell’s substrate. For instance we have shown that dynamic compressive loading in a porous polymer scaffold triggers human mesenchymal stem cells to differentiate into bone cells just as well as commonly used soluble inducers of bone differentiation. We have shown that even very low magnitude mechanical strains can induce cell differentiation if applied at very high frequencies (60Hz). In collaboration with Orla protein Technologies we are investigating which peptide sequences of bone growth factors such as bone morphogenetic protein 2 (BMP-2) will induce stem cell differentiation in serum free conditions, to avoid the use of animal derived serum when culturing these cells. We also collaborate with colleagues at Jageillonian University, Krakow, Poland on how to improve growth factor response of stem cells and induce differentiation by bioactive materials.