To Identify Small Molecules that Stimulate Appendage Tissue Regeneration

Nearly 2 million people in the United States are living with limb loss, either due to disease or to trauma. Unlike humans, zebrafish can regenerate much of their lost tissue. In preliminary studies, we identified the phosphatase PTPT1B as a critical regulator of tissue regeneration. In the absence of PTP1B, regeneration of both appendage and heart tissue is enhanced by 2-fold. In an effort to identify small molecules that could enhance regenerative capacity, we screened newly synthesized analogs of PTP1B inhibitors in the highly regenerative caudal fin system. We amputated adult wildtype caudal fins, introduced candidate compounds and then imaged regenerative growth at 4 days post-amputation (dpa). In a series of studies, we have identified 4 inhibitors of PTP1B activity that show promising augmentation of appendage regeneration. While these are promising initial results, additional studies are needed to confirm these findings and to identify an optimal effective dose. Nonetheless, our results raise the intriguing possibility that these compounds may improve the limited regenerative potential in humans.