Prometheus' vulture and the promise of stem cells
N. Rosenthal, A. Musaro
Mouse Biology Programme, European Molecular Biology Laboratory, via Ramarini 32, 00016 Monterotondo (Rome), ITALY
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.
Key words:
Stem cells, muscle, aging, injury, regeneration
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