Regeneration and pattern formation in planarians III. Evidence that neoblasts are totipotent stem cells and the source of blastema cells

In most regenerating systems, blastema cells arise by dedifferentiation of functional tissue cells. In planarians, though, it is still debatable whether dedifferentiated cells or a population of undifferentiated cells, the neoblasts, are the main source of blastema cells. Moreover, it is unclear whether in the intact organisms neoblasts are quiescent cells 'reserved' for regeneration or if they serve as functional stem cells of all differentiated cell types. Both uncertainties partly stem from the failure to distinguish by conventional labelling methods neoblasts from differentiated cells. Here we describe a new approach to these problems based on testing the regenerative and stem cell capabilities of purified neoblasts and differentiated cells when introduced, separately, into irradiated hosts. Introduction of neoblasts led to resumed mitotic activity, blastema formation, and extended or complete survival of the host; differentiated cells, in contrast, never did so. Therefore, planarian neoblasts can be qualified as totipotent stem cells and the main source of blastema cells, while dedifferentiation does not seem to operate either in intact or regenerating organisms. In addition, these results strengthen the idea that different types of regeneration and blastema formation, linked to the tissular complexity of the organisms, are present in the animal kingdom.