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Advanced Drug Delivery Reviews (v.57, #13)
Embryonic stem cell science and the therapeutic interface
by Colin W. Pouton Theme Editor; Tim Allsopp Theme Editor (pp. 1891-1893).
Embryonic stem cells: Understanding their history, cell biology and signalling by Ruairi Friel; Sjaak van der Sar; Patrick J. Mee (pp. 1894-1903).
Embryonic stem cells offer enormous potential as a source of a variety of differentiated cells for cell therapy, drug discovery and toxicology screening. With the creation of human embryonic stem cell lines we now have a resource with the potential to differentiate into every tissue of the body. To fully harness this resource it is necessary to understand their biology. Here we give a background to their history, describe interesting elements of their cell biology and introduce the underlying signalling mechanisms that control their ability to self-renew and differentiate.
Keywords: Embryonic; Stem cell; History; Biology; Signalling; Review; Drug discovery; Toxicology; Cell therapy
ES cell technology: An introduction to genetic manipulation, differentiation and therapeutic cloning by Lilian Hook; Carmel O'Brien; Timothy Allsopp (pp. 1904-1917).
ES cells are extraordinary cells, capable of proliferating in a pluripotent state indefinitely and of differentiating spontaneously into all cell types in vivo and many in vitro. However, the manipulation and modification of ES cells by processes such as directed differentiation and genetic modification have placed ES cells at the forefront of many biological studies and could lead to their application in biopharmaceutical areas such as cellular therapy and drug screening. Here we describe some of the ES cell based technologies that have lead to this realisation of ES cell potential.
Keywords: Lineage selection; Gene targeting; Differentiation; Drug discovery; Cell therapy
Pharmaceutical applications of embryonic stem cells by Colin W. Pouton; John M. Haynes (pp. 1918-1934).
Embryonic stem cells (ESCs) will become a source of all adult differentiated cells once reliable protocols for directed differentiation have been established. This resource will revolutionise laboratory cell biology and will provide much improved cell culture models for discovery and development of drugs, and fundamental studies of the genetic basis of disease. These are early days, and there are few examples of practical outcomes in the pharmaceutical world, though in recent years some drug-like molecules, which direct differentiation, have been discovered. At this stage the focus is on understanding the signalling systems and transcription factors that drive differentiation, on characterisation and isolation of precursor cells, and on establishing methods to improve the homogeneity of differentiated cells derived from ESCs. There is particular interest in establishing methods for deriving fully differentiated human cells from human ESCs (HESCs), but there are challenges to be met before HESC technology can be taken up in a widespread manner. Protocols for expansion of HESC cultures are labour-intensive at present. There is an urgent need for discovery of factors that will allow serum-free (and feeder cell-free) expansion of HESCs, and which can be applied to the majority of HESC lines. Our expectation is that adequate protocols will emerge in the coming years opening the way for development of many cell culture tools in the pharmaceutical industry. Here we review the current status and future prospects for this exciting field and encourage pharmaceutical scientists to play a role in directing its development.
Keywords: Embryonic stem cells; Pharmaceutical applications; Differentiation; Drug discovery; Low molecular weight drugs; Drug screening
Embryonic stem cells: Meeting the needs for cell therapy by Maria Teresa Mitjavila-Garcia; Clémence Simonin; Marc Peschanski (pp. 1935-1943).
Cell therapy in diverse organs has bloomed for degenerative diseases over the past decade, following a previous period of development in which haematopoietic stem cells grafts in oncology were its most prominent clinical application. One main limitation that has, however, been encountered on the path for transforming pioneering successes into real therapeutics, that would be applicable to a clinically relevant number of patients, is the difficulty in accessing “therapeutic� cells, such as foetal neurons in neurodegenerative diseases, adult pancreatic β cells in diabetes or else myoblasts in heart failure and myopathy. The future of cell therapy definitely belongs to cell banks, from which physicians would simply have to draw according to their needs. However, besides haematopoietic stem cells, for which such infrastructures begin to exist for clinical purposes (in particular from cord blood), cell banks are still up to now essentially a scientific concept. This review focuses on the possibility for human ES cells to meet both the requirements of cell banking and the needs for substitutive cell therapy.
Keywords: Degenerative diseases; Cell implantation; Transplantation immunology; Cell differentiation; Cell migration
Transplanting stem cells: Potential targets for immune attack. Modulating the immune response against embryonic stem cell transplantation by Ashleigh S. Boyd; Yasuyuki Higashi; Kathryn J. Wood (pp. 1944-1969).
The curative promise of stem cells and their descendants for tissue regeneration and repair is currently the subject of an intense research effort worldwide. If it proves feasible to differentiate stem cells into specific tissues reliably and safely, this approach will be invaluable in the treatment of diseases that lead to organ degeneration or failure, providing an alternative or supplementary source of tissue for transplantation. Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of a pre-implantation blastocyst that can produce all cells and tissues of the foetus. In recent years, several laboratories have described the directed differentiation of ES cells into multiple mature cell types including: cardiomyocytes; haemopoietic cells; hepatocytes; neurones; muscle cells and both endocrine and exocrine cells of the pancreas. How the immune system of the host will respond when these ES cell-derived mature cells are transplanted is ill defined. This review will focus on the potential mechanisms that the immune system could use to target ES cell-derived transplants and how unwanted responses might be prevented.
Keywords: Abbreviations; Ab; antibody; EB; embryoid body; ES; embryonic stem cellsES cells; Stem cell transplantation; Immunogenicity; Rejection
Legal and ethical status of stem cells as medicinal products by Lincoln Tsang (pp. 1970-1980).
The realisation of the full potential of products based on stem cells in a clinical setting demands robust scientific evidence, underpinned by legitimate regulatory requirements to ensure their safety and efficacy. This review examines the legal aspects of the use of stem cells in the laboratory and in the development of new therapies and pharmaceutical products. UK and European legal and regulatory documents and directives are used as the framework for discussion of the current status and future prospects.
Keywords: Stem cells; Legal status; Ethics; Regulatory status
The UK Stem Cell Bank: Its role as a public research resource centre providing access to well-characterised seed stocks of human stem cell lines by Lyn Healy; Charles Hunt; Lesley Young; Glyn Stacey (pp. 1981-1988).
The rapidly expanding field of stem cell research offers the potential to develop therapeutic agents to treat diseases such as Parkinson's, diabetes and heart disease. It is important that stem cell lines derived from quality-controlled and well-characterised cell banks should be made available to both the scientific and clinical communities to promote high-quality research and development. The requirement in the United Kingdom (UK) for rigorous regulation of the procurement and use of embryonic stem (ES) cell lines led the UK government to fund the establishment of a national bank for stem cell lines. The UK Stem Cell Bank (UKSCB) hosted at the National Institute for Biological Standards and Control (NIBSC) is committed to working closely with the clinical and research communities to provide qualified stocks of human stem cell lines of adult, foetal and embryonic origin for both research use and for use in emerging human therapy.
Keywords: UKSCB; Stem cells; Banking; Quality; Regulation; Facilities