Media-fuelled belief that stem cells possess a virtually unlimited restorative power and represent a universal remedy for all diseases has resulted in considerable funding support and scientific progress in stem cell biology over the last decade. However, despite exciting prospects, the potential of stem cells has not yet materialized. Patients with serious degenerative disorders such as Parkinson's disease, diabetes or cardiac disease have been waiting for the fulfilment of these media-hyped promises, but as yet there are a relatively small number of clinical trials despite years of research in this field.
Most commonly, embryonic stem cells (ESCs) are generated from the inner cell mass of the blastocyst (). In vitro these appear to be immortal, proliferating indefinitely in an undifferentiated, pluripotent state (). However, ESCs in vivo lose this property as differentiation proceeds and as development and growth-promoting signals change. By adulthood, the few remaining stem cells are dispersed throughout the body and are difficult to locate. However, they seem to be able to continue to generate identical daughter cells and/or tissue cells at each division. These residual pools of stem cells are suggested to be the source of the tissue regeneration and repair that occurs in adults. Tissue-specific stem cells are present in many organs and systems in adult animals although they differ greatly in their ability to self-renew and differentiate. For example, spermatogonial stem cells in the testis are unipotent and produce only one type of differentiated cell—the spermatozoon. By contrast, mesenchymal stem cells are multipotent and can produce adipocytes, osteoblasts, chondrocytes and myocytes in appropriate culture conditions. Unlike their embryonic counterparts, tissue-specific stem cells are not immortal, and show a decreasing capacity to self-renew with increasing age. This limitation has been associated with the reduced ability to repair the damage that accumulates with ageing, possibly owing to exhaustion of the stem cell pool, or as a consequence of inherited or acquired mutations throughout life that impede normal stem cell function.
Most commonly, human embryonic stem cells are derived from inner cell mass (ICM) of the blastocyst plated on mitotically inactivated fibroblasts.
Human embryonic stem cell (hESC) colony. hESCs have high alkaline phosphatase activity (green). Actin filaments (red) are visualized with rhodamine X-conjugated phalloidin in both hESCs and surrounding human foreskin fibroblast feeders.
The difficulty in locating these scarce stem cells from a variety of sources and expanding their number sufficiently for therapeutic use is proving a major hindrance for industry in the translation of stem cell potential to be used in regenerative medicine. Pluripotent stem cells, both human ESCs (hESCs) and induced pluripotent stem cells (iPSCs), are exceptions since they can be produced in theoretically limitless quantities, and therefore capable of providing more cells than from any other source, regardless of differentiation efficacy and stabilization. Thus, they are the cell type likely to yield the most from invested capital. Although both types of stem cells are promising, there are still a number of unresolved technical and biological issues that make iPSCs less likely to be the immediate choice for cell-based therapy. This leaves the pluripotent hESCs as the best stem cell model for capital investment for stem cell therapy.
The initial difficulties with legislation to allow use of human embryos for stem cell research, the lack of consensus for reporting the quality and type of embryos suitable for stem cell derivation, and the route to translation have largely been overcome, especially in the UK, where a regulatory route map to facilitate clinical application has recently been produced as a collaborative project between the regulatory bodies involved: Human Fertilisation and Embryology Authority (HFEA), Human Tissue Authority (HTA) and Medicines and Healthcare Products Regulatory Agency (MHRA).