ABSTRACT
BACKGROUND: Chronic allograft vasculopathy (CAV) is an important cause of graft loss. Considering the immune inflammatory events involved in the development of CAV, therapeutic approaches to target this process are of relevance. Human amniotic fluid-derived stem cells (hAFSCs), a class of fetal, pluripotent stem cells with intermediate characteristics between embryonic and adult stem cells, display immunomodulatory properties. hAFSCs express mesenchymal and embryonic markers, show high proliferation rates; however, they do not induce tumor formation, and their use does not raise ethical issues. Thus, we sought to investigate the effect of hAFSC on CAV in a model of aorta transplantation. METHODS: Orthotopic aorta transplantation was performed using Fisher (F344) rats as donors and Lewis rats as recipients. Rats were divided into three groups: syngeneic (SYNG), untreated F344 receiving aorta from F344 (n = 8); allogeneic (ALLO), Lewis rats receiving allogeneic aorta from F344 (n = 8); and ALLO + hAFSC, ALLO rats treated with hAFSC (10(6) cells; n = 8). Histological analysis and immunohistochemistry were performed 30 days posttransplantation. RESULTS: The ALLO group developed a robust aortic neointimal formation (208.7 ± 25.4 µm) accompanied by a significant high number of ED1+ (4845 ± 841 cells/mm2) and CD43+ cells (4064 ± 563 cells/mm2), and enhanced expression of α-smooth muscle actin in the neointima (25 ± 6%). Treatment with hAFSC diminished neointimal thickness (180.7 ± 23.7 µm) and induced a significant decrease of ED1+ (1100 ± 276 cells/mm2), CD43+ cells (1080 ± 309 cells/µm2), and α-smooth muscle actin expression 8 ± 3% in the neointima. CONCLUSIONS: These preliminary results showed that hAFSC suppressed inflammation and myofibroblast migration to the intima, which may contribute to ameliorate vascular changes in CAV.
Subject(s)
Amniotic Fluid/cytology , Aorta, Abdominal/transplantation , Aortic Diseases/prevention & control , Fetal Stem Cells/transplantation , Organ Transplantation/adverse effects , Pluripotent Stem Cells/transplantation , Actins/metabolism , Animals , Aorta, Abdominal/immunology , Aorta, Abdominal/metabolism , Aorta, Abdominal/pathology , Aortic Diseases/etiology , Aortic Diseases/immunology , Aortic Diseases/metabolism , Aortic Diseases/pathology , Biomarkers/metabolism , Cell Movement , Cells, Cultured , Fetal Stem Cells/immunology , Fetal Stem Cells/metabolism , Humans , Immunohistochemistry , Male , Myofibroblasts/metabolism , Myofibroblasts/pathology , Neointima , Pluripotent Stem Cells/immunology , Pluripotent Stem Cells/metabolism , Rats , Rats, Inbred F344 , Rats, Inbred Lew , Time FactorsABSTRACT
OBJECTIVE: To determine the accuracy and practicality of fetal echocardiography in the identification of structural and functional cardiac abnormalities prior to 16 weeks' gestation in fetuses with increased nuchal translucency thickness (NT). METHODS: Between January 1996 and June 2002 early fetal echocardiography using the transvaginal route was performed at 12-16 weeks' gestation on 275 fetuses with increased NT. The abnormal cardiac findings were classified as either structural (congenital heart defects) or functional, defined as transient phenomena which might later disappear, such as isolated tricuspid regurgitation and an enlarged ascending aorta. The abnormal findings were related to pregnancy outcome, including autopsy results, karyotyping results, and late fetal and neonatal echocardiography. RESULTS: Cardiac abnormalities were present in 61 fetuses overall (22.2%); including structural cardiac defects in 37 fetuses (13.5%) and functional abnormalities in 24 fetuses (8.7%). Structural cardiac abnormalities were associated with abnormal karyotype in 24 fetuses and normal karyotype in 13 fetuses. Of the 24 fetuses with functional cardiac abnormalities, 2 (8.3%) had isolated tricuspid regurgitation and 22 (91.7%) had enlarged ascending aorta. Abnormal karyotype was present in this group in 4 cases (16.7%). CONCLUSION: Increased NT can be used to define a high-risk group that should receive specialized early fetal echocardiography. This is a reliable technique with great potential for the diagnosis of both structural and functional cardiac abnormalities.
