About Models of Regeneration

Regeneration is arguably among the most inspiring biological phenomena known to exist. The history of the Western canon is populated by many examples of the indiscriminate, powerful grip regeneration has exerted on the human mind. For instance, when Lazzaro Spallanzani reported in 1768 that decapitated snails regenerate their heads, scientists, philosophers and the public alike scoured their gardens in an attempt to replicate this fascinating experiment (Odelberg, 2004). It was also discovered that salamanders can regenerate limbs and tails (including the spinal cord), while planarians can regenerate entire animals from small body fragments. Despite the longstanding interest in this biological problem, and the knowledge that animals from all walks of life perform regenerative feats, we are still in the early stages of describing these events in cellular, molecular, and mechanistic terms. However, the genetic and molecular tools to address the problem of regeneration are rapidly improving. Aside from the curiosity it normally elicits, the study and understanding of regeneration could dramatically impact the practice of medicine.

Just as relevant is the understanding derived from the investigation of stem cells, undifferentiated cells that have the capacity to replace themselves indefinitely and to produce specialized cell types. While embryonic stem cells divide and ultimately give rise to all the differentiated cell types of the body, adult stem cells from specific tissues are normally lineage restricted to a specific set of cell types. In order for an adult animal to replace missing structures with an exact copy of what is missing, it is clear that developmental programs must be redeployed. However, the dynamics of cell communication and proliferation are vastly different, as are the cell types involved. To accomplish regeneration, adult animals may invoke the proliferation of differentiated cells, the activation of reserve stem cells, the formation of new stem cells with limited capacity to self renew (progenitor cells), or a combination of these strategies.

Which cells in an adult animal divide and differentiate to replace the multiple cell types required during a regenerative response? While this is a very basic, indeed, fundamental question that has been formulated and reformulated through successive generations of biologists, its resiliency against experimental attacks has proved surprising, and in many cases quite frustrating. Nonetheless, it is apparent that different tissues use different strategies to achieve tissue repair or regeneration. For example, the vertebrate liver invokes compensatory regeneration after the removal of two lobes, whereby the remaining lobe proliferates to reacquire the original tissue mass without replacing the missing lobes. In fact, regeneration can be compensatory (liver), tissue-specific (heart, skeletal muscle, liver, pancreas, lens, retina), or it can rebuild complex structures containing multiple tissue and organ types (e.g., limbs, fins, tails). The goal of researchers studying model organisms of regeneration is to discover how these animals naturally accomplish the seemingly impossible task of restoring body parts lost to trauma.