Going out on a limb about regrowing an arm

Buddy D. Ratner

Starting with the observations that fetuses effortlessly grow limbs, fetuses heal wounds without scar and children up to the age of two can partially regrow amputated digits, the potential for adult humans to regrow limbs is explored. The process of limb growth in amphibians is reviewed with these steps summarizing the process: blood vessels contract to minimize bleeding; the injury site is covered by skin cells transforming into the apical epithelial cap which sends signals important for the next phases of the regrowth; resident fibroblasts leave the surrounding extracellular matrix and migrate across the amputation surface; migratory fibroblasts proliferate and dedifferentiate to form an aggregation of stemlike cells called the blastema; and the blastema coordinates the formation of a new limb. Other factors contributing to this process are: innervation, cell spatial "memory," chemical signals between cells, gene up and down regulation, cell differentiation (or dedifferentiation) and inflammatory cells. Remarkable discoveries have been made in all these areas in the last few years that might be integrated into technology for limb regeneration. In particular, the demonstration of the plasticity of supposedly "terminally differentiated" cells speak to the idea that mature cells at the amputation site might be harnessed for limb regrowth. Also, the demonstration that macrophages can be driven to a regenerative phenotype (M2) and they may also be stem-like is promising for complex regenerations. This article posits that scientific discoveries useful for limb regeneration have been made and now it is time to develop technology exploiting these discoveries to regrow limbs.