ABSTRACT
Rationale: Human induced pluripotent stem cell-derived endothelial cells can be candidates for engineering therapeutic vascular grafts. Methods: Here, we studied the role of three-dimensional culture on their characteristics and function both in vitro and in vivo. Results: We found that differentiated hPSC-EC can re-populate decellularized biomatrices; they remain viable, undergo maturation and arterial/venous specification. Human PSC-EC develop antifibrotic, vasoactive and anti-inflammatory properties during recellularization. In vivo, a robust increase in perfusion was detected at the engraftment sites after subcutaneous implantation of an hPSC-EC-laden hydrogel in rats. Histology confirmed survival and formation of capillary-like structures, suggesting the incorporation of hPSC-EC into host microvasculature. In a canine model, hiPSC-EC-seeded onto decellularised vascular segments were functional as aortic grafts. Similarly, we showed the retention and maturation of hiPSC-EC and dynamic remodelling of the vessel wall with good maintenance of vascular patency. Conclusions: A combination of hPSC-EC and biomatrices may be a promising approach to repair ischemic tissues.
Subject(s)
Induced Pluripotent Stem Cells , Pluripotent Stem Cells , Animals , Blood Vessel Prosthesis , Cell Differentiation , Dogs , Endothelial Cells/metabolism , Humans , Induced Pluripotent Stem Cells/metabolism , RatsABSTRACT
INTRODUCTION: Many studies have explored that thyroid dysfunctions can be induced by cytokine therapy. Most observations were collected in connection with the treatment of viral hepatitis with interferon-alpha. AIM AND METHODS: Frequency and types of thyroid dysfunction developed during and after recombinant interferon-alpha treatment were studied in 138 patients with viral hepatitis C or B. Therapy lasted 12 months or more, subjects having thyroid dysfunction at the start of therapy were excluded from the study. Thyroid parameters (TSH, FT4, FT3 and anti-TPO) were controlled every third month. In patients in whom thyroid dysfunction occurred the measurements were repeated monthly and other tests were also performed (anti-Tg, IL-6, TSH receptor antibody, thyroid scan and 99mTc-pertechnetate uptake). RESULTS: Thyroid function disturbances were found in 30 (21.7%) patients, 12 of them (8.7%) showed persistent hypothyroidism. Hyperthyroidism was transitory in all cases. The clinical course of thyroid dysfunction might be monophasic (hyper- or hypothyroidism), biphasic (hyperthyroidism followed by hypofunction) or triphasic. Immune and non-immune forms can be clearly distinguished. CONCLUSIONS: Every fifth patient with chronic hepatitis showed thyroid dysfunction during interferon-alpha therapy, it is necessary therefore to control the hormonal status and the thyroid antibody titer. Treated patients have to be informed in advance that as a "side effect" persistent hypothyroidism may develop.
