Stem cells are an important resource for tissue repair and regeneration. While a 
great deal of attention has focused on derivation and molecular regulation of 
stem cells, relatively little research has focused on how the subcellular 
structure and composition of the cell membrane influences stem cell activities 
such as proliferation, differentiation and homing. Caveolae are specialized 
membrane lipid rafts coated with caveolin scaffolding proteins, which can 
regulate cholesterol transport and the activity of cell signaling receptors and 
their downstream effectors. Caveolin-1 is involved in the regulation of many 
cellular processes, including growth, control of mitochondrial antioxidant 
levels, migration and senescence. These activities are of relevance to stem cell 
biology, and in this review evidence for caveolin-1 involvement in stem cell 
biology is summarized. Altered stem and progenitor cell populations in 
caveolin-1 null mice suggest that caveolin-1 can regulate stem cell 
proliferation, and in vitro studies with isolated stem cells suggest that 
caveolin-1 regulates stem cell differentiation. The available evidence leads us 
to hypothesize that caveolin-1 expression may stabilize the differentiated and 
undifferentiated stem cell phenotype, and transient downregulation of caveolin-1 
expression may be required for transition between the two. Such regulation would 
probably be critical in regenerative applications of adult stem cells and during 
tissue regeneration. We also review here the temporal changes in caveolin-1 
expression reported during tissue repair. Delayed muscle regeneration in 
transgenic mice overexpressing caveolin-1 as well as compromised cardiac, brain 
and liver tissue repair and delayed wound healing in caveolin-1 null mice 
suggest that caveolin-1 plays an important role in tissue repair, but that this 
role may be negative or positive depending on the tissue type and the nature of 
the repair process. Finally, we also discuss how caveolin-1 quiescence-inducing 
activities and effects on mitochondrial antioxidant levels may influence stem 
cell aging.