Neoblasts in Turbellaria

Der Recent success in the production of human embryonic stem cells has gained enormous scientific and public interest because of the potential of the cells to differentiate into all cell types. Research on human embryonic stem cells has raised controversy on ethical and social questions. Therefore, studying also other stem cell systems is needed for a better understanding of the basic molecular and cell biological properties of totipotent or pluripotent cells. Within the animal kingdom the flatworms (Platyhelminthes) possess an extraordinary stem cell system. Comparatively little is known about cell dynamics of this system in spite of the recently revived interest in these animals and their key position in the phylogenetic tree of organisms. At least for the subgroup of the planarian flatworms it has been shown that apparently totipotent stem cells (neoblasts) are the only source for cell renewal and regeneration also in adult animals. We have found that the flatworm Macrostomum sp.that is a member of one of the most basal taxa of flatworms and is very accessible to experiments at the cellular level because of its small size and its tranparency, possesses a similar stem cell system. In studies of this project we have applied bromodeoxyuridine labeling to show the distribution, migration, and differentiation of S-phase neoblasts in this species. We have ultrastructurally characterized neoblasts in different stages of differentiation. Cell cycle progression was studied using S-phase and mitosis double labeling in combination with colchicine treatment to arrest mitosis in metaphase. Cell dynamics during postembryonic development and during starvation and feeding periods were analyzed. Programmed cell death was studied to trace the loss of cells by apoptosis during the course of cell renewal. In order to obtain markers for investigating cell differentiations, monoclonal antibodies against various cell types of Macrostomum have been produced. A monoclonal antibody library with about 200 different Hybridoma clones is now available. In addition, the regeneration of the muscle system after transversal cutting has been traced, using a specific muscle marker. The embryonic development of Macrostomum sp. has been addressed For comparison, the number and distribution of proliferating cells has been demonstrated in the acoel flatworm Convolutriloba longifissura. The extraordinary mode of asexual reproduction of C. longifissura has been investigated and published in a collaborative work. In summary, the studies have shown that stem cells differentiate into several different cell types and that a subpopulation of stem cells remains totipotent in adult animals. On this basis it will be possible to contribute with our continuing project to a better understanding of the nature of stem cells, of pattern formation, regeneration and evolution of tissues in this basal group of metazoans.