STRUCTURAL ORGANIZATION OF RECONSTITUTED HUMAN ARTERIAL SMOOTH-MUSCLETISSUE

We used human arterial smooth muscle cells (SMCs) that had been reorga nized three-dimensionally into aggregates, so-called spheroids, as a m odel system that might more closely correspond to arterial smooth musc le in vivo than do conventional monolayer cultures. After reaggregatio n the presence of serum in the culture medium strongly promoted the ma intenance of spheroidal SMCs. With access to fresh serum, the spheroid s developed into highly organized structures with an outer laminated s hell of spindle-shaped SMCs and a more porous core of rounded or polyg onal SMCs. After several weeks in culture, extracellular matrix compon ents appeared and the tissue assumed features characteristic of maturi ng intimal repair tissue. Many cells had features of programmed cell d eath (apoptosis). This feature may be important because it may indicat e 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 situat ion in vitro resembles that of atherosclerotic tissue in vivo, in whic h retention of plasma constituents is a conspicuous feature. In some r espects, therefore, the small sample of human arterial tissue represen ted by the spheroid may represent an in vitro analogue of the arterial wall, which may undergo maturation or degenerative atherosclerosis-li ke changes depending on exogenous factors. The spheroidal SMC system m ay therefore also be a suitable model for in vitro studies of atheroge nesis.