Conclusions and Future Prospects

The use of human tissue is increasingly difficult due to increasing regulations. In addition, the variability of such materials limits their value for drug development and toxicology. It is to be hoped that cell-based systems will increasingly use human cell lines, many of which have qualities yet to be fully realized through the application of cell differentiation protocols and three-dimensional (3-D) cell culture methods. A number of cell differentiation protocols are available that can be used to enhance the performance of cell lines as models of tissue, and these may include the treatment of cultures with bioactive molecules [40] or 3D culture systems [41].

Nanotechnology and systems for single cell analysis may well provide new approaches to the rapid generation of data on the response of cells to drugs and toxicants [42-44]. Another area currently generating great interest is that of embryonic stem cell lines to provide a diverse range of differentiated cell types as models of human tissue for drug testing and toxicology [45]. Although stem cell testing has been under development for in-vitro assays for some years [46], mouse embryonic cell lines have been used more recently [47-49]. Test methods using human embryonic stem cell (hESC) lines are also being developed, and hESCs are beginning to be investigated as tools for developmental toxicology [49, 50]. Potentially, the hESC offer systems that in many countries are fundamentally more acceptable when compared to other technologically advanced sources of embryonic tissue such as zebra fish embryos [51, 52].

A number of research groups are currently generating hESC lines from cells used in the prenatal diagnosis of inherited disorders and which carry genetic defects predisposing to known diseases [53]. Such lines have significant potential in generating in-vitro tissue models that could significantly enhance our ability to investigate therapeutic drugs for inherited genetic diseases such as cystic fibrosis.

At present, however, the culture of hESC lines remains very difficult, and the standardization of data is hampered by the significant levels of differentiated cells that arise in each new culture (see Table 9.4). Nonetheless, when the basic methods of culture and control of differentiation are mastered, these cultures can be expected to provide valuable methods for drug screening and toxicology. Significantly, a number of initiatives have already been launched to develop the standardization of hESC cultures [54, 55]. Hopefully these developments, combined with the biological potential of hESC, will deliver new and improved systems for in-vitro testing and drug development.

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