Does fetal hepatocyte transplantation provide metabolic support immediately after surgically induced acute hepatic failure in rats?
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Tarih
1999
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info:eu-repo/semantics/openAccess
Özet
Akut karaciğer yetmezliği yüksek mortalite oranı ile alakalıdır. Akut karaciğer yetmezliği (AKY) olan hastalarda cerrahi yaklaşım ortotopik karaciğer transplantıdır. Ancak bu yaklaşım birçok risk ve zorluk içerir. Eğer yetmezliğin kritik döneminde uygun destek tedavisi verilirse karaciğer rejenere olma ve kendiliğinden iyileşme fırsatını bulabilir. Bu çalışmada %90 hepatektomi ile AKY yetmezliği oluşturulan Wistar Albino sıçanlarda intrasplenik fetal hepatosit transplantasyonunun metabolik destek sağlaması değerlendirildi. Sıçanlar aşağıdaki gibi dört gruba ayrıldı. Grup 1. AKY’den 4 ay önce fetal hepatositler (0.1 ml Fetal Hepatosit (FH) süspansiyonu, 2x106 hücre) dalak içine transplante edildi. Grup 2. Fetal hepatositler AKY ile aynı zamanda transplante edildi. Grup 3. Hank’in dengeli tampon solüsyonu dalak içine enjekte edildi ve 4 ay sonra AKY oluşturuldu. Grup 4. Hank’ın dengeli tampon solüsyonunun enjeksiyonu ile AKY oluşturulması aynı zamanda yapıldı. Mortalite oranları, kan glukoz seviyeleri ve dalağın histopatolojik görünümü değerlendirildi. Grup 2, 3 ve 4’deki hayvanların hepsi 5 gün içinde öldü, grup 1’de 2 hayvan öldü, beşi ise yaşadı. Grup 1’de kan glukoz seviyeleri diğerlerine göre anlamlı olarak yüksekti. Hepatositlerin makroskopik nodülleri ve dalak içindeki mikroskopik organize hepatositler sadece grup 1’de gözlendi. Grup 2, 3 ve 4 ile kıyaslanınca grup 1’deki anlamlı yaşamda kalma oranları fonksiyon gören hepatositlerin sağladığı desteğe bağlıdır. Sonuç olarak AKY’den önce yapılırsa fetal hepatosit transplantasyonu hayatta kalma oranını iyileştirmektedir.
Acute hepatic failure (AHF) is associated with a high mortality rate. The surgical approach for patients with AHF is orthotopic liver transplantation. However, this approach involves many risks and difficulties. If proper supportive therapy is given during the critical period of failure the liver may have the opportunity to regenerate and recover by itself. In this study, intrasplenic fetal hepatocyte (FHc) transplantation was evaluated for providing metabolic support in Wistar Albino rats with AHF produced by 90% hepatectomy. We divided the rats into four groups as follow: Group 1: Fetal hepatocytes (0.1 ml of FHc suspension: 2x106 cells) were transplanted into the spleen 4 months before AHF. Group II: Fetal hepatocytes were transplanted to the spleen at the same time of induced AHF. Group III: Hank's balanced buffer solution (HBBS) was injected into the spleen and 4 months later AHF was induced. Group IV: HBBS was injected into the spleen and AHF was induced at the same time. We evaluated mortality rates, blood glucose levels and histological appearance of the spleen. All animals in groups II, III and IV died in five days whereas two animals died and five animals survived in group I. In group I, blood glucose levels were significantly higher than the others.Macroscopic nodules of hepatocytes and microscopically organized hepatocytes were seen in spleen only in group I. The significant improvement of survival rates in group I compared to groups II- III-IV is due to the net support provided by functioning hepatocytes. We therefore conclude that FHc transplantation provides metabolic support and improves survival rate if performed prior to AHF.
Acute hepatic failure (AHF) is associated with a high mortality rate. The surgical approach for patients with AHF is orthotopic liver transplantation. However, this approach involves many risks and difficulties. If proper supportive therapy is given during the critical period of failure the liver may have the opportunity to regenerate and recover by itself. In this study, intrasplenic fetal hepatocyte (FHc) transplantation was evaluated for providing metabolic support in Wistar Albino rats with AHF produced by 90% hepatectomy. We divided the rats into four groups as follow: Group 1: Fetal hepatocytes (0.1 ml of FHc suspension: 2x106 cells) were transplanted into the spleen 4 months before AHF. Group II: Fetal hepatocytes were transplanted to the spleen at the same time of induced AHF. Group III: Hank's balanced buffer solution (HBBS) was injected into the spleen and 4 months later AHF was induced. Group IV: HBBS was injected into the spleen and AHF was induced at the same time. We evaluated mortality rates, blood glucose levels and histological appearance of the spleen. All animals in groups II, III and IV died in five days whereas two animals died and five animals survived in group I. In group I, blood glucose levels were significantly higher than the others.Macroscopic nodules of hepatocytes and microscopically organized hepatocytes were seen in spleen only in group I. The significant improvement of survival rates in group I compared to groups II- III-IV is due to the net support provided by functioning hepatocytes. We therefore conclude that FHc transplantation provides metabolic support and improves survival rate if performed prior to AHF.
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19
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2