Mechanically challenged tissue-engineered organs, such as blood vessels, traditionally relied on synthetic or modified biological materials for structural support. In this report, we present a novel approach to tissue-engineered blood vessel (TEBV) production that is based exclusively on the use of cultured human cells, i.e., without any synthetic or exogenous biomaterials. Human vascular smooth muscle cells (SMC) cultured with ascorbic acid produced a cohesive cellular sheet. This sheet was placed around a tubular support to produce the media of the vessel. A similar sheet of human fibroblasts was wrapped around the media to provide the adventitia. After maturation, the tubular support was removed and endothelial cells were seeded in the lumen. This TEBV featured a well-defined, three-layered organization and numerous extracellular matrix proteins, including elastin. In this environment, SMC reexpressed desmin, a differentiation marker known to be lost under standard culture conditions. The endothelium expressed von Willebrand factor, incorporated acetylated LDL, produced PGI2, and strongly inhibited platelet adhesion in vitro. The complete vessel had a burst strength over 2000 mmHg. This is the first completely biological TEBV to display a burst strength comparable to that of human vessels. Short-term grafting experiment in a canine model demonstrated good handling and suturability characteristics. Taken together, these results suggest that this novel technique can produce completely biological vessels fulfilling the fundamental requirements for grafting: high burst strength, positive surgical handling, and a functional endothelium.
Mechanically challenged tissue-engineered organs, such as blood vessels, traditionally relied on synthetic or modified biological materials for structural support. In this report, we present a novel approach to tissue-engineered blood vessel (TEBV) production that is based exclusively on the use of cultured human cells, i.e., without any synthetic or exogenous biomaterials. Human vascular smooth muscle cells (SMC) cultured with ascorbic acid produced a cohesive cellular sheet. This sheet was placed around a tubular support to produce the media of the vessel. A similar sheet of human fibroblasts was wrapped around the media to provide the adventitia. After maturation, the tubular support was removed and endothelial cells were seeded in the lumen. This TEBV featured a well-defined, three-layered organization and numerous extracellular matrix proteins, including elastin. In this environment, SMC reexpressed desmin, a differentiation marker known to be lost under standard culture conditions. The endothelium expressed von Willebrand factor, incorporated acetylated LDL, produced PGI 2 , and strongly inhibited platelet adhesion in vitro. The complete vessel had a burst strength over 2000 mmHg. This is the first completely biological TEBV to display a burst strength comparable to that of human vessels. Short-term grafting experiment in a canine model demonstrated good handling and suturability characteristics. Taken together, these results suggest that this novel technique can produce completely biological vessels fulfilling the fundamental requirements for grafting: high
Functional gastrointestinal disorders (FGID) can benefit from various psychological interventions. The main objective here was to define the contribution of a new psychotherapeutic intervention, group counseling psychotherapy, for the management of FGID patients. Secondary aims included validation of new measures for gastrointestinal symptoms and quality of life in patients with FGID. Fifty patients seen in a tertiary care center were included in a program of 10 weekly sessions of 2 hr each. Gastrointestinal symptoms, quality of life, and psychological conditions were measured before and after treatment by quantitative indices and by qualitative self-analysis. Gastrointestinal index and quality-of-life index were significantly (P < 0.02) improved at the end of the psychotherapeutic intervention (from 77.5 +/- 4.0 to 63.2 +/- 4.3 and from 67.7 +/- 3.9 to 54.9 +/- 3.9, respectively). In a control group of patients observed for a comparable period of time while waiting for the psychotherapy program, gastrointestinal and quality of life indices remained unchanged. The severity of gastrointestinal symptoms and the quality of life deterioration were highly correlated factors (r = 0.8) at entry into the trial, and their improvement with psychotherapy was also correlated (r = 0.6; P < 0.001). Psychological abnormalities were frequent in these patients (anxiety in 31%, somatization in 29%, depression in 26% of the patients). However, no specific disorder could predict the results of the psychotherapeutic intervention. Over the long term (6-24 months after conclusion of treatment), gastrointestinal status, quality of life, and psychological condition were estimated as improved by 53%, 63%, and 67% of the patients, respectively. The gastrointestinal index and quality of life index we developed were validated to detect the disease and to follow its evolution in response to treatment. In conclusion, group counseling psychotherapy offered a significant contribution for the management, improving gastrointestinal symptoms and quality of life, of FGID patients. New measures for symptom severity and quality of life are available.
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