N. Rosenthal, A. Musaro

When Prometheus transgressed the will of the ancient gods to steal fire for mankind, Jupiter had the great Titan chained to the side of Mount Caucasus where a vulture preyed daily on his liver, which was renewed as quickly as it was devoured. We mere mortals do not possess so vigorous a regenerative capacity, but the legend captures well the remarkable potential of certain mammalian tissues to rebuild themselves. Tissue-restricted regeneration might explain why some organs, lacking a sufficiently robust progenitor cell population, do not regenerate as well as others. This concept has been challenged by mounting evidence for populations of progenitor cells, perhaps set aside during gestation, that can contribute to virtually any tissue type under appropriate experimental conditions and might be coerced into renewed regenerative service in later life. We have discovered that myogenic progenitors were enhanced in regenerating transgenic mouse muscle expressing an Insulin-like Growth Factor 1 (mIGF-1) isoform, which maintains tissue integrity during exercise and aging, counters muscle decline in degenerative disease, and enhances healing following injury. Elevated recruitment of proliferating bone marrow cells to injured mIGF-1 muscles was accompanied by increased bone marrow stem cell production revealing an unexpected response to distal trauma. Damaged transgenic muscles activated novel gene sets typical of urodele amphibian regeneration, and expressed chemoattractants used in homing of metastatic tumour cells. Thus, supplemental growth factors can amplify the local stimulus of injury or degeneration, by mobilizing uncommitted stem cells to target and rebuild damaged tissues in a Promethean paradigm of self-renewal.

Keywords (Optional): 
Stem cells