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We used human arterial smooth muscle cells (SMCs) that had been reorganized three-dimensionally into aggregates, so-called spheroids, as a model system that might more closely correspond to arterial smooth muscle in vivo than do conventional monolayer cultures. After reaggregation the presence of serum in the culture medium strongly promoted the maintenance of spheroidal SMCs. With access to fresh serum, the spheroids developed into highly organized structures with an outer laminated shell of spindle-shaped SMCs and a more porous core of rounded or polygonal SMCs. After several weeks in culture, extracellular matrix components appeared and the tissue assumed features characteristic of maturing intimal repair tissue. Many cells had features of programmed cell death (apoptosis). This feature may be important because it may indicate that regression of arterial smooth muscle tissue may be a much more strongly controlled process than hitherto realized. Without access to fresh serum, the spheroidal tissue showed degenerative features, much like those in atherosclerotic lesions, ie, the presence of foam cells, cellular debris, and some cell death. It is possible that this situation in vitro resembles that of atherosclerotic tissue in vivo, in which retention of plasma constituents is a conspicuous feature. In some respects, therefore, the small sample of human arterial tissue represented by the spheroid may represent an in vitro analogue of the arterial wall, which may undergo maturation or degenerative atherosclerosis-like changes depending on exogenous factors. The spheroidal SMC system may therefore also be a suitable model for in vitro studies of atherogenesis.

Structural organization of reconstituted human arterial smooth muscle tissue.