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Bone from blood: Optimised isolation, characterisation and osteogenic induction of mesenchymal stem cells from umbilical cord blood

Final Report Summary - OSTEOCORD (Bone from blood: Optimised isolation, characterisation and osteogenic induction of mesenchymal stem cells from umbilical cord blood)

Stem cells are 'blank' cells that can replicate indefinitely, or given the right triggers, grow into specialised cells for specific areas of the body. In adults, a few types of cell, such as blood, bone marrow or nerves, are unable to replicate themselves by normal cell division. Within these parts of the body, a small quantity of stem cells is found, that is used to repair and replace damaged cells. The intrinsic ability of stem cells to self-repair on demand has generated a significant level of interest in determining how scientists might be able to exploit stem cells for the treatment of certain disease conditions. There is an urgent clinical requirement for appropriate bone substitutes that are able to replace current grafting procedures for the repair of diseased or damaged bone. Mesenchymal stem cells (MSCs) are found predominantly in the bone marrow and are able to differentiate into osteogenic (bone), chondrogenic (cartilage), adipogenic (fat) and tenogenic (tendon) tissue types, thus offering considerable therapeutic potential for tissue engineering applications in orthopaedic surgery. However, invasive extraction procedures and poor cell yields have demanded the identification of alternative tissue sources of MSCs. Growing evidence suggests that umbilical cord blood (UCB) contains a population of rare MSCs that are able to give rise to many different cell types in a manner similar to bone marrow-derived MSCs. The aim of this project was to optimise the isolation and expansion of MSCs from human UCB (CBMSCs). The differentiation capacity of CB-MSCs will be examined, with a specific focus on osteogenesis, and we will tissue engineer three-dimensional (3-D) bone replacement structures.

OSTEOCORD was a nine-partner project funded by the European Commission's Seventh Framework Programme (FP7) with representatives from academia and industry. The CB-MSCs was characterised using a range of techniques, including examination of the gene and protein expression profiles, before and after osteogenic differentiation, compared to MSCs isolated from human bone marrow, as well as embryonic stem cells. The integrated datasets allowed the consortium to identify specific and / or novel signalling pathways associated with CBMSCs, this helped them to understand CB-MSC biology and may help identify new targets for cell-based therapies. Bioimpedance measurements of CB-MSCs in two-dimensional (2- D) and 3-D growth configurations were determined, using purpose-built microchips for high throughput characterisation. The immune status of CB-MSCs was also determined. Allogeneic transplantation of MSCs between different individuals may be possible, as MSCs appear to be 'immune-privileged', in that they are not necessarily rejected when implanted into unmatched recipients. It is important to point out that MSCs display immuno-suppressive characteristics, and are able to reduce an immune response and promote the engraftment of different cell types, such as skin cells and blood cells. Therefore, it was necessary to determine how CB-MSCs react under different immune environments. To deliver sufficient cell numbers for viable therapies, key components of the project focused on expansion protocols. Comparative analyses of growth rates and ageing characteristics will identify the lifespan of CB-MSCs in culture. Novel techniques were combined with scale-up procedures and the generation of CB-MSC lines for banking, following optimised cryopreservation protocols. Biocompatibility assays using a range of bespoke, bio mimetic scaffolds were used to develop tissue engineering applications. An independent ethical evaluation of the work determined how the work has contributed to the ethics of stem cell research and other issues such as cord blood banking. OSTEOCORD also provided a social science assessment of the different expectations of MSCs held across the research community. The aim was to assist the research community in better understanding broader technical, regulatory, commercial and clinical factors in the future shaping of MSCs, and articulate, robust and empirically informed scenarios for the exploitation of MSCs.

Since its launch, the OSTEOCORD project and all of its work packages have gained ground. The major achievements are set out below:
- determined growth characteristics and CD antigen expression profile of CB-MSCs, following recovery from cryopreservation;
- determined electrochemical impedance measurements of BM-MSCs, using a planar electrode chip system;
- developed BM-MSC spheroids for 3-D electrode chip assays;
- optimisation of MSC alloreactivity assays in progress;
- analysed dynamic microcarrier-assisted bioreactors for CB-MSC growth;
- established osteogenic differentiation protocols;
- identified candidate osteogenic scaffolds and initiated biocompatibility studies;
- completed an extensive international patents review, on the therapeutic applications of MSCs.

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