Force generation of different human cardiac valve interstitial cells: relevance to individual valve function and tissue engineering.
OBJECTIVE
Cardiac valves perform highly sophisticated functions that depend upon the specific characteristics of the component interstitial cells (ICs). The ability of valve ICs to contribute to these functions may be related to the generation of different types of tension within the valve structure. The study aim was to characterize cellular morphology and the forces generated by valve ICs and to compare this with morphology and forces generated by other cell types.


METHODS
Cultured human valve ICs, pericardial fibroblasts and vascular smooth muscle cells were seeded in 3-D collagen gels and placed in a device that accurately measures the forces generated. Cell morphology was determined in seeded gels fixed in glutaraldehyde, stained with toluidine blue and visualized using a high-definition stereo light microscope.


RESULTS
Valve ICs generated an average peak force of 30.9 +/- 10.4 dynes over a 24-h period which, unlike other cell types tested, increased as cell density decreased (R = 0.67, p <0.0001). The temporal pattern of force generation in mitral valve cells was significantly faster than in aortic or tricuspid cells (p <0.05). Microscopic examination revealed the formation of cellular processes establishing a cell/cell and cell/matrix network. When externally induced changes in matrix tension occurred, the valve ICs unlike the other cell types - did not respond to restore the previous level of tension.


CONCLUSIONS
Human cardiac valve ICs produce a specific pattern of force generation that may be related to the individual function of each heart valve. The specialized function of these cells may serve as a guide for the choice of candidate cells for tissue engineering heart valves.
Smith
Sally
S
Heart Science Centre, National Heart and Lung Institute, Imperial College at Harefield Hospital, Harefield, Middlesex, UK.
Taylor
Patricia M
PM
Chester
Adrian H
AH
Allen
Sean P
SP
Dreger
Sally A
SA
Eastwood
Mark
M
Yacoub
Magdi H
MH
D000293:Adolescent; D000328:Adult; D000368:Aged; D018929:Cell Culture Techniques; D002648:Child; D002675:Child, Preschool; D003239:Connective Tissue Cells / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D006351:Heart Valves / Q000166:cytology* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D010496:Pericardium / Q000166:cytology; D012501:Saphenous Vein / Q000166:cytology; D023822:Tissue Engineering