'Hearts and bones': the ups and downs of 'plasticity' in stem cell biology

Abstract

More than a decade ago, 'plasticity' suddenly became a 'fashionable' topic with overemphasized implications for regenerative medicine. The concept of 'plasticity' is supported by old transplantation work, at least for embryonic cells, and metaplasia is a classic example of plasticity observed in patients. Nevertheless, the publication of a series of papers showing rare conversion of a given cell type into another unrelated cell raised the possibility of using any unaffected tissue to create at will new cells to replace a different failing tissue or organ. This resulted in disingenuous interpretations and a reason not to fund anymore research on embryonic stem cells (ESc). Moreover, many papers on plasticity were difficult to reproduce and thus questioned; raising issues about plasticity as a technical artefact or a consequence of rare spontaneous cells fusion. More recently, reprogramming adult differentiated cells to a pluripotent state (iPS) became possible, and later, one type of differentiated cell could be directly reprogrammed into another (e.g. fibroblasts into neurons) without reverting to pluripotency. Although the latter results from different and more robust experimental protocols, these phenomena also exemplify 'plasticity'. In this review, we want to place 'plasticity' in a historical perspective still taking into account ethical and political implications.

Figure 1. Cell reprogramming

1. Nuclear transfer into an anucleated oocyte reprograms a somatic nucleus, thus generating a blastocyst from which ES cells can be derived.

2. Cell fusion exposes two different nuclei to the same cytoplasm, and one nucleus may impose its transcriptional program (red) over the other (blue).

3. Transfer of specific transcription factors may reprogram a somatic cell (yellow) to a pluripotent (iPS) or to another differentiated cell type (red).

4. Transplantation of a genetically labeled (blue nucleus) differentiated cell (red) to a different tissue (yellow) may activate that developmental program in the transplanted cell.

Figure 2. Changing the model of cell determination and differentiation

Grey arrows indicate the ability of ES and iPS cells to give rise to germ and somatic layers, that proceed (light blue arrows) towards their various differentiated tissues. Green arrows represent the possibility of reprogramming differentiated cells to a pluripotent state or directly to a different differentiated cell type, independently from the germ layer of origin.