Generation of somatic cells by direct conversion - do we need pluripotent cells?

Abstract

Th e pluripotency of embryonic stem cells (ESCs) makes them a potentially attractive resource for generating clinically useful somatic cells except for the problem of immune rejection. In eff ect, a transplant of cells diff erentiated from an ESC line is no diff erent than receiving cells from the individual that would have developed from the embryo that from which the ESCs were originally derivedfrom. In view of this, it should not be surprising that the recipient's immune system could attempt to reject the incoming foreign cells. Th is is the primary reason why techniques to make individualised human pluripotent stem cells hhave been intensively investigated over the last twenty years. Initial attempts focused on the possibility of therapeutic cloning, the deliberate creation of a human embryo by transfer of a somatic nucleus from the intended recipient into an oocyte from a human donor, with the aim of creating a tailor-made stem cell line from that embryo's inner cell mass;, however, this method has not yet been successful (1,2). Th erapeutic cloning may indeed have been rendered obsolete by the technique of induced pluripotency (3,4), and if the products of this method, namely induced pluripotent stem cells or iPSCs, are truly equivalent to ESCs, this could be the way to usher in the long promised age of personalised regenerative medicine. Th ere are still substantial problems to overcome before this becomes reality. Even if iPSCs and ESCs are equivalent, we still need to develop reproducible methods to direct their diff erentiation into clinically useful cells or tissues in a cost-eff ective manner. Moreover, we must ensure that the resulting cells are functionally equivalent to their adult body counterparts and do not create additional health problems years after their administration. In short, there is still much work to be done.