Derivation of clinical grade embryonic stem cell lines in Manchester

During in vitro fertilisation (IVF) treatment many eggs and embryos fail to develop normally and are unsuitable for clinical use and routinely discarded at an early stage. Other embryos are frozen for future use. The purpose of this research is to use these eggs and embryos, with appropriate patient consent, to make human embryonic stem cells. Embryo stem cells are special cells that appear to be able to develop into all cells found in the body. As such they can be used to study early embryo development, how specialized cells form or deteriorate, to test drugs for toxicity, or for therapeutic use in the treatment of degenerative disease or tissue damage. Although many human embryonic stem cell ?lines? exist throughout the world, these are all research grade and are unlikely to be suitable for treatment of diseases. The aim of the proposed research is therefore to make new embryonic stem cells under highly regulated and clinically clean conditions, suitable for transplantation. We have new IVF and stem cell laboratories built and run to these standards and the current proposal requests funding to maintain and run these facilities in order to maximise the production of clinical grade embryonic stem cells. These new cell lines will be deposited in the UK Stem Cell Bank and any clinical treatments and commercial exploitation organised by Central Manchester NHS Trust and the University of Manchester together with the Medical Research Council.

The purpose of this proposal is to derive and fully characterise 6-8 new clinical grade human embryonic stem cell (hESC) lines. It will extend the operation of the currently funded NW Embryonic Stem Cell Centre (NWESCC) in Manchester until 2011 in order to fulfil this aim. Recently established GMP cleanroom laboratory facilities funded by the MRC (IVF laboratories at St Mary?s Hospital) and the NW Development Agency (hESC laboratories at the University of Manchester) will be used. Our existing expertise in patient consenting, embryology, derivation and characterisation of hESC lines, Quality Management, and regulatory issues will be exploited and built upon. This will be extended via links and collaborations with other centres eligible for this work, including Edinburgh/Roslin Cells, Nottingham, King?s London, and Birmingham. Embryos from three sources will be used for derivation, including (i) surplus embryos from fresh IVF cycles, (ii) immature or failed-to-fertilise oocytes activated with chemical/parthenogenetic stimuli, and (iii) high quality embryos cryopreserved at the pronucleate stage. Over the last 12-18 months a large number of oocytes and embryos have been donated from the IVF programmes at St Mary?s and Manchester Fertility Services, leading to the derivation of 3 well established research grade hESC lines, RCM-1 (in collaboration with Roslin Cells, Edinburgh), Man-1 and Man-2, the first two of which have been submitted to the UK Stem Cell Bank. Clinical grade lines will be derived employing our established standard operating procedures which will be developed and refined. These make use of significant advances by NWESCC in the areas of xeno-free derivation and culture, feeder-free culture media and a GMP human fibroblast feeder cell line. Regulatory compliance will be maintained via our established Quality Management system and in conjunction with intellectual property departments at the University of Manchester and CMMC NHS Trust who will assist with commercial exploitation of GMP hESC lines in conjunction with MRC.