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A virtually unlimited supply of hepatocytes for transplantation, bio-artificial livers and drug testing would be highly desirable. If stem cell biology is to fulfil its potential and deliver this dream, then certain requirements must be met. Stem cell-derived “hepatocytes” should be readily available from an ethically acceptable source, tolerate cryopreservation allowing “off the shelf” use, demonstrate adequate metabolic and synthetic activity and, if transplanted should functionally integrate with non-parenchymal cells in the liver. Most importantly, cell transplantation must be safe. Derivation from an autologous source, thereby overcoming immunological barriers would further increase the applicability of this potential therapy.
There is a growing number of potential starting cell populations from which one may potentially derive hepatocyte-like cells (for a comprehensive review, see Oertel and Shafritz1). Broadly speaking the starting cell populations may be developmentally “primitive” such as the embryonic stem cells or be more differentiated such as foetal hepatocytes. Generally, the more primitive the starting cell population, then the greater is the potential to expand in culture the numbers of cells available for use. The challenge with such cells is to accurately control their differentiation into mature cells types such as hepatocytes and control their subsequent proliferation so that unwanted tumours do not form. Embryonic stem cells have an almost unlimited capacity for proliferation and have the ability to form all cell types – so-called pluripotentiality. However, the current use of embryonic stem cell derived tissues for transplantation is hampered by the potential of these cells to form tumours. Induced pluripotent stem cells have been an extremely exciting innovation from the Yamanaka laboratory.2 By over-expressing certain transcription factors …
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