Enabling technologies for human embryonic stem cell micro-monitoring and expansion: steps towards stem cell therapy

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Human embryonic stem (hES) cell technology offers remarkable scope for the development of
new therapies for a diverse range of diseases, including degenerative diseases such as
cardiovascular, musculoskeletal and neurodegenerative diseases, as well as diabetes and tissue damage caused by injury. In addition hES cell research provides novel opportunities for drug discovery and testing, and new inroads into human developmental biology.
There are several major challenges facing successful delivery of hES cell-based therapeutics to
the clinic. These include i) derivation of a large number of well-characterised hES cell lines; ii)
micro-monitoring of potency versus differentiation; iii) rapid and efficient scaling-up of hES cell
cultures, iv) overcoming the requirement for animal reagents for sustained ES cell maintenance,
and v) providing a three-dimensional environment for stem cell growth and differentiation. This
proposal addresses these problems using a combination of the principles and methods of
engineering and cell biology.
The technology will provide a platform for the micro-analyses of conditions required to sustain
pluripotency versus differentiation in several hES cell lines in parallel. Miniaturisation of culture
systems will be achieved using parallel perfused micro-bioreactors which can readily be
incorporated with a multiphoton microspectral imaging system for non-invasive in situ
monitoring. Variables such as pH and lactate can be measured on-line, and detection of specific
protein markers in very small numbers of cells by fluorescent tags. New methods of expansion of
hES cells will be tested in rotational wall and hollow fibre membrane bioreactors, successfully
used previously for expansion of heamopoietic and neural stem cells.
A major focus of current stem cell research is on factors required to drive hES cells along specific
differentiation pathways and streamlining the basic stem cell technology is under-researched. The much-heralded therapeutic, clinical application of hES cell biology will not be feasible without
substantial improvements in successful hES cell derivation, monitoring and expansion to
overcome the problems highlighted above. The results from this research will represent
significant steps towards bringing stem cell technology closer to the clinic. The potential impact of the research outlined in this proposal on human health and our knowledge of human tissue
development and function could therefore be substantial.
The research proposed here is highly innovative and cross-disciplinary, involving the application
of a combination of state-of the-art engineering and stem cell biology methodologies. The
research is essentially non-hypothesis driven, and as such is likely to be unsuitable for traditional routes for grant funding.