Cell sources for skeletal tissue engineering
Cells can be obtained fairly easily from many types of mature tissue; for example, simple enzyme treatments can be used to digest the collagen matrix to release cartilage cells. These cells do, however, have two inherent problems. Firstly, it has been found that mature cells loose their characteristic abilities when expanded in culture, so it becomes increasingly difficult to convert them back into functioning tissues as the quantity of engineered tissue is increased. Secondly, we commonly need engineered tissue to rectify disease, in elderly patients there may not be any pristine tissue left to sample for suitable cells...
Working with mature cells introduces a number of tissue engineering problems. These cells are not normally permitted to proliferate in the body (this behaviour is characteristic of many types of cancer). When required the body calls upon stocks of 'stem cells', which differentiate to produce the tissue required.
As a consequence considerable research effort is being mobilised to identify and isolate suitable stem cells. These cells should, in theory, be ideal for a programme of expansion followed by differentiation into the desired tissue type. Most stem cells in the body, however, appear to be pre-programmed to make given types of tissues. Currently we are studying a range of stem cell 'niches' with colleagues at the University of Leeds, trying to identify the best sources of stem cells for given tissue types. For example, bone marrow is a good source of stem cells, but experiments and experience show that they convert into osteoblasts very readily, and considerable effort must be made to prevent them from doing this if another tissue outcome is desired.
One of the problems with introducing engineered tissue into a diseased environment is that the new tissue is likely to be adversely effected by this environment. As a consequence, we have teamed up with colleagues in the School of Medicine to evaluate genetic engineering possibilities for cells in vitro. In particular, we are attempting to up-regulate the inhibition of metalloproteinases in chondrocytes. Metalloproteinases are enzymes that break down the extracellular material, and are implicated in erosive joint disease. Our preliminary experiments have shown that this genetic modification does help to protect cartilage in an inflammatory environment in vitro.
Researchers engaged in this work are Richard Ackbar, Dr Mike D. Barker (School of Medicine), Dr Aileen Crawford, Prof. Paul Hatton, Elenor Jones (University of Leeds), Agnieszka Kwarciak and Denis McGonegal (University of Leeds)