Stimulating Regeneration in Mouse Limbs

DESCRIPTION (provided by applicant): Some vertebrate animals, mainly amphibians, can regenerate their limbs after amputation. While mammals, including humans, are generally considered to have lost this regenerative capacity, the prospect of human limb regeneration is encouraged by the observation that the human and mouse fingertips are able to regenerate. The mouse digit has recently become a good mammalian model for regeneration studies because the regeneration characteristics of the mouse digit closely resemble that in humans. There have been attempts to enhance regeneration in the mouse digits, but so far it remains unsuccessful for mid-phalanx amputations. In ongoing studies on limb regeneration in the anuran amphibian, Xenopus laevis, we have successfully stimulated limb regenerate by transplantation of limb progenitor cells in a fibrin gel patch, provided with exogenous factors tha promote growth and provide patterning information to the cells. However it remains to be determined whether progenitor cells can also be utilized to stimulate regeneration in mammals and humans. In this project we will test the hypothesis that with appropriate combination of cells and growth factors we can stimulate regeneration of the amputated mouse digit. We will determine the conditions for mouse embryonic limb progenitor cells to enhance digit regeneration by optimizing the delivery method and growth factors used. We will also establish protocols for generating limb progenitor cells from induced pluripotent stem (iPS) cells. We anticipate that this study will demonstrate that limb progenitor cells have the ability to participte in and to promote mammalian digit regeneration. It will also reveal the optimal treatment of progenitor cells with growth factors and small molecules for transplantation. The findings will contribute to the development of a progenitor cell based treatment for human finger and limb injuries in the future.