Group leader: 

Paul A De Sousa

Position: 

Associate Researcher

Contact: 

Paul [dot] desousa [at] ed [dot] ac [dot] uk

Feel the love in the De Sousa lab - © Eirini Koutsouraki
Aims
To understand and control the growth and pluripotency of human embryo stem cells so as to enable their use in regenerative medical therapies. Specifically, this is achieved through studies focused on i) their epigenetic stability, ii) signalling pathways controlling self-renewal and survival, and iii) the identification of biochemically equivalent molecular substitutes for poorly defined animal and human sourced reagents currently use in cell culture.

Background
While human stem cells can be sourced from a range of embryonic through to adult tissues, those derived from preimplantation embryos remain unmatched for their capacity for growth and differentiation. These properties provide human embryo stem cells (hESCs) with excellent long-term prospects for curative therapies for a range of conditions which currently cannot or are struggling to be met by transplantation of adult or fetal derived tissues or alternative therapies. Realising the therapeutic promise of hESCs requires that they be isolated, cultured, manipulated, banked, and delivered to recipients in a quality assured manner compliant with existing and emerging national and international regulatory standards.

Delivery of hESCs and their derivatives safely to the clinic, must also overcome significant challenges in the in vitro culture systems used to sustain and manipulate them. First, these must produce sufficient quantities of functionally normal cells that are immunologically tolerable, or can be made tolerable to the recipient. Secondly, cells that are produced must be free of contaminants or pathogens that could harm the individual or be transmitted to the general population, respectively.

To date nearly all hESC lines that have been derived have been directly exposed to at least one animal sourced product (i.e. cells, blood serum, serum components, or purified protein). Our own previous research has yielded 6 new hESC lines, one of which is the first to be isolated in chemically defined media with only indirect exposure to an animal sourced product, namely an animal serum fraction, during the preparation of human helper cells used to support stem cell growth.

Approaches and progress
The lab is engaged in multiple collaborations providing complimentary expertise to our own in hESC culture.

These include:

Prof Adrian Bird, Director of Welcome Trust for Cell Biology, and Dr Simon Tomlinson, CRM, in the characterisation of hESC epigenetic stability through bioinformatic evaluation of an unbiased global screen for variations in CpG island methylation.

Prof Robert Millar, Director, and Dr Adam Pawson of MRC Human Reproductive Sciences, in characterising a role for G-protein signalling in hESC growth and self-renewal.

Prof Mark Bradley, Department of Chemistry, University of Edinburgh, in the identification of polymers providing a supportive substrate for hESC growth.

Prof Mark Head, CJD Surveilance Unit, Prof Marc Turner, SNBTS/UoE, and Prof Jean Turner, Neuropathogenesis unit- Roslin Institute, in the evaluation of a role for PrP in hESC self-renewal, survival and disease transmission.

One opportunity for translation of research output is through Roslin Cells Ltd, a company established to derive Quality Asssured Research and Clinical Grade Human Embryo Stem Cells. Dr Paul de Sousa co-founded Roslin Cells Ltd and serves as Chief Scientific Officer.

The lab is also coordinating the BEST Stem Cells project, a European research collaboration aimed at developing safe, efficient growth and storage technologies for human embryonic and adult mesenchymal stem cells for therapeutic use.

Selected publications

• Anderson RA, Bayne RAL, Gardner J, De Sousa PA. 2009. Brain-derived neurotrophic factor (BDNF) is a regulator of human oocyte maturation and early embryo development. Fertility and Sterility, in press, doi:10.1016/j.fertnstert.2009.04.007.
• De Sousa PA, Gardner J, Sneddon S, Pells S, Jorgenson Tye B, Dand P, Collins DM, Steward K, Shaw L, Przyborski S, Cooke M, McLauglin KJ, Kimber SJ, Lieberman BA, Wilmut I, Brison D. 2009. Clinically failed eggs as a source of normal human embryo stem cells. Stem Cell Research, in press, PubMed 19393594.
• Franklin SB, Hunt C, Cornwell G, Peddie V, De Sousa PA, Livie M, Stephenson EL, Braude PR. 2008. hESCCO: development of good practice models for hES cell derivation. Regen Med 3(1):105-116.
• De Sousa PA and Wilmut I. 2007. Human parthenogenetic embryo stem cells: appreciating what you have when you have it. Cell Stem Cell 1(3):243.
• De Sousa PA. 2006. Optimising the therapeutic safety of human embryonic stem cells through the evolution of defined culture systems supporting their isolation. Expert Opinion. Biol Ther 6:551-554.
• De Sousa PA, Galea G, Turner M. 2006. The road to providing human embryo stem cells for therapeutic use: the UK experience. Reproduction 5:681-689.

Funding
Chief Scientist Office (Scotland)
Medical Research Council (MRC)
Scottish Enterprise Edinburgh and Lothian