What controls organ regeneration?

Abstract

What controls organ regeneration? This is one of the 125 big questions of Science 125th anniversary. And it is one of the most important 25 questions. Many organisms have remarkable regeneration ability, such as earthworm, turbellarian, Gekko japonicas and newt. Unfortunately, all of them are in the bottom of phylogenetic tree, the more higher the loss of this kind of magic. What controls this program? The research of this problem not only could tell us where are we from? Why we are? The most important is the answer would decide our future: it is the dream of developmental biologist and medicine research, all of us. Regeneration means the self-repair and replacement of the organism after the partial structure has been lost. Or recover the shape, structure and function of the original organs after the injury. Some lowly creatures can regenerate damaged organs completely. For example, planarian, cut it from the center, it would become two individuals. In fact even cut it into 279 pieces, it would become 279 individuals. This magic comes from a special kind of cell: neoblasts. These kind of adult stem cells diffuse distribution in the whole body of planarians. As long as the existence of such a cell, they can regenerate a whole planarian. Newt is the master of regeneration in vertebrates. Its limbs, tail, heart, jaw, brain, and retina and lens can be completely regenerated. There is not a fraction of difference of morphology and function of tissue and organ between the original and the regeneration. There are different regeneration mechanisms. The young Japanese salamander often uses stem/progenitor cells in its tissues to regenerate limbs, After adult they use their skeletal muscles to differentiate or transdifferentiate. Despite young or old, all of Salamanders have the common powerful ability of regeneration. By contrast, the regenerative capacity of Xenopus gradually loses as it grows. Early tadpole can regenerate their limb, the late tadpoles and adult Xenopus that after metamorphosis cannot regenerate absolutely. With the evolution, the ability of regeneration is lost step by step. Just like the process of development of embryo, as differentiation becomes more complex, more and more functional, the more loose of pluripotent. Humans, as mammals, retain only a small capacity of regeneration. Replacing damaged, diseased and senescent parts of the human body is always one of humanity's dreams. The discovery of induced pluripotent stem cells has enabled us to move cells back to their infancy, provide us a useful tool and material to investigate the organ regeneration. But what we know about the mechanism of human regeneration is still very limited. It can be said that 11 years have passed, we have learned a lot, but it is far from enough to reach the goal.