Regeneration is the ability to replace damaged or lost cells, tissues or parts of the body. It is widespread across the animal kingdom, but the capacity to regenerate varies greatly between different animals. Some examples of animals with high regenerative abilities are: starfish (arm), fish (tail fin), and salamanders (limb). Extreme cases like hydra and planarians can even regenerate a complete new organism out of a small tissue fragment. While mammals and humans cannot replace a missing limb, the body is able to regenerate a wide range of injured tissues and organs, such as for example the skin, blood, bone, and gut. The methods of regeneration of different tissues within a body and among different species can be very different. However, they have in common that they rely on the activity of stem cells.
Stem cells are cells which, under the right conditions, can divide to form two daughter cells. These daughter cells either become new stem cells in order to maintain the stem cell pool (self-renewal), or they mature into specialized cells with a specific function, e.g. blood cells, muscle cells, bone cells, …. (differentiation). Importantly, stem cells are the only cells in the body which can generate new cell types. The ability to generate different cell types is called potency. In general, stem cells are divided in 4 classes based on their potency. 1) Totipotent stem cells can form any of the cell types of the extra-embryonic and embryonic tissues. These are present in the early embryo of humans. 2) Pluripotent stem cell can generate most, but not all cell types. 3) Multipotent stem cells can produce only a few different cell types, e.g. the different types of blood cells. 4) Unipotent stem cells can only form a single cell type. The adult human body contains multipotent and unipotent stem cells, and some of these cells appear to be involved, at least in part, in repair and regeneration of damaged tissues.
Researchers are fascinated by regeneration and stem cells in order to develop regenerative medicine, which aims at the improvement of tissue repair and maintenance. However, the knowledge of how regeneration works and how stem cells function is still very incomplete, and many questions remain. Why can some animals regenerate so much better than others? What kind of cell features and mechanisms exist during regeneration? Are there shared molecular pathways between the regeneration process of different animals and humans? How can we boost regeneration in human tissues?
To study how regeneration and stem cells actually work, researchers study specific types of animals, that are commonly called model organisms. Planarians are a type of free-living flatworms (Platyhelminthes) that is used in the laboratory as a model organism. They are mainly found in freshwater, but some also live in marine environments and even on land. They are soft-bodied worms and contain complex tissues and organ systems, such as photoreceptors (eyes), a small brain, a digestive system, epidermis, and muscle. The internal organs are surrounded by mesenchymal tissue. Within this tissue lie the stem cells that are called neoblasts. Neoblasts are the only somatic proliferating cells in the flatworm body.
Planarians are very motile and move via the coordinated movement of cilia (small hairs) at their ventral epidermis. They dislike light and often reside in the shadow. In nature, they can often be found under stones at the edge of rivers or ponds. The worms eat living or dead small animals which they suck up with their muscular pharynx.
Planarians have been established as a system for studying regeneration over 200 years ago. Even today, they are popular model organisms for studying regeneration and stem cells. One of the most studied species is Schmidtea mediterranea. Interestingly, S. mediterranea has both a sexual strain and asexual strain. The sexual worms reproduce as cross-fertilizing hermaphrodites. This means that these sexual worms have both male and female reproduction organs (gonads), but they do have to fertilize each other as 1 individual cannot fertilize itself. After fertilization, the sexual worms will develop and lay cocoons containing multiple eggs. These will develop into juvenile worms before hatching from the cocoon. In contrast, the asexual worms reproduce by transverse fission. During fission, the worms stretches itself, becoming longer and thinner, until the worms divides into 2 fragments. The fission always happens in the posterior two thirds of the worm, just behind the pharynx. Both fragments will regenerate the missing tissues, resulting in 2 worms. The asexual strain of S. mediterranea is the most commonly used in the laboratory and is the strain provided in our Science Boxes. Importantly, both the sexual and asexual strain have the same regeneration capacity.
Schmidtea mediterranea can regenerate a complete animal from almost any fragment of the body. This impressive regeneration capacity is made possible by an abundant population of neoblasts. The neoblasts represent the stem cells of flatworms. This stem cell population includes pluripotent stem cells, called clonogenic neoblasts (cNeoblasts) and fate-specified cells (specialized neoblasts which are multi- or unipotent). This is in contrast to mammals and humans who do not have pluripotent stem cells in the adult body. After amputation, the neoblasts will increase their proliferation rate and their daughter cells will accumulate at the wound area forming an unpigmented mass of new tissue which is called the blastema. In this blastema, orchestrated differentiation will take place. Eventually this will restore all lost tissues and organs. At the same time, old tissue will undergo remodeling to facilitate the integration of the newly formed tissue with the preexisting one. The resulting animal will be smaller than the original, and will therefore grow after regeneration has completed. Eventually, a properly proportioned and functioning new animal will be formed.
Besides regeneration, the neoblasts are used to maintain adult tissues. Aged and damaged cells are constantly removed and replaced by newly differentiated cells formed by the neoblasts. As a consequence, animals can live for many years and the asexual strain of S. mediterranea is even claimed to be immortal thanks to this efficient cell turnover.