RESUMO
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.
Assuntos
Líquido Amniótico/citologia , Aorta Abdominal/transplante , Doenças da Aorta/prevenção & controle , Células-Tronco Fetais/transplante , Transplante de Órgãos/efeitos adversos , Células-Tronco Pluripotentes/transplante , Actinas/metabolismo , Animais , Aorta Abdominal/imunologia , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Doenças da Aorta/etiologia , Doenças da Aorta/imunologia , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Biomarcadores/metabolismo , Movimento Celular , Células Cultivadas , Células-Tronco Fetais/imunologia , Células-Tronco Fetais/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Neointima , Células-Tronco Pluripotentes/imunologia , Células-Tronco Pluripotentes/metabolismo , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Fatores de TempoRESUMO
BACKGROUND: Alloantigen mismatch and cold ischemia have been shown to induce transplant arteriosclerosis. Pravastatin (PR) decreases arteriosclerosis probably related to an immunosuppressive effect. Statins possess other nonimmune properties that may be beneficial to transplantation. We studied the effect of PR on cold ischemia and alloantigen-induced transplant arteriosclerosis in syngeneic (SYN) and allogeneic (ALLO) aortic transplantation models. METHODS: Lewis rats served as the donors and recipients for SYN transplants and Brown Norway rats were donors for ALLO transplants. Aortic segments that had been preserved at 4 degrees C in Euro-Collins solution for 0 or 24 hours were transplanted to the infrarenal aorta of the recipients PR (10 mg/kg/d) was administered for 12 weeks prior to morphometric studies. Areas of intimal thickness and its relation to total vessel area were calculated. Lipid levels were measured at 12 weeks. RESULTS: Aorta rings preserved for 24 hours showed marked intimal thickening compared to controls (SYN, CI 0 hours = 21.5% +/- 16.5% vs SYN, CI 24 hours = 50.7 +/- 9.5%, P <.05). PR significantly decreased thickening (SYN, CI 24 hours + PR = 41.7 +/- 12.2 (P <.05) vs SYN, CI 0 hours on SYN, CI 24 hours). There was a nonsignificant decrease in thickening among ALLO transplants treated with PR (ALLO = 31.4 +/- 15.9 vs ALLO + PR = 23.8 +/- 18.8; P >.05). PR had no effect on lipid levels. PR decreases cold ischemia induced transplant arteriosclerosis in this syngeneic aortic transplant model, but does not affect an alloantigen-mediated process. The beneficial effect of PR is not related to its lipid-lowering properties but probably to a nonimmune effect.
Assuntos
Aorta Abdominal/transplante , Arteriosclerose/prevenção & controle , Pravastatina/farmacologia , Transplante Homólogo/fisiologia , Animais , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/patologia , Arteriosclerose/etiologia , Temperatura Baixa , Modelos Animais de Doenças , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Isquemia , Isoantígenos , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante Homólogo/patologia , Transplante Isogênico/patologia , Transplante Isogênico/fisiologia , Túnica Íntima/patologiaRESUMO
Although veins and arteries present similar wall structures, there are differences which may be relevant in peripheral nerve reconstruction. Inside-out vein grafts (IOVG) have been satisfactorily used to repair both motor and sensitive nerves. However, the inside-out artery graft (IOAG) is a new technique and not fully investigated. Our study presents comparative morphological data on nerve regeneration achieved with IOVG and IOAG in the repair of Wistar rat sciatic nerves. Jugular veins and aorta arteries were harvested from donor animals and used "inside-out" to bridge a 10-mm gap. Animals were sacrificed at 10 weeks to evaluate nerve regeneration. Both techniques presented great variability in nervous tissue, though some animals showed satisfactory results. Different intensities of scarring processes might have interfered with nerve regeneration. Although IOVG and IOAG techniques showed similar morphometric results, in general, IOVG presented a closer-to-normal nerve organization than IOAG.