Efficacy of autologous mesenchymal stem cell transplantation in patients with liver cirrhosis

Abstract

Background/Aims: Because of several limitations and complications of liver transplantation, new alternative treatment modalities are required for patients with liver cirrhosis. Many study results encourage the use of autologous bone marrow-derived mesenchymal stem cells for liver diseases. In this study, we assessed the impact of autologous mesenchymal stem cell transplantation on liver tissue and liver chemistry. Materials and Methods: Twenty-five patients with biopsy-proven liver cirrhosis were enrolled in the study. Patients received 1×10 6 autologous mesenchymal stem cells/kg via a peripheral vein. Biochemical parameters were checked monthly. Periodical radiological screening and liver biopsies before mesenchymal stem cell transplantation were performed after 6 months. Liver specimens were assessed by a pathologist. Results: No side effect was observed and the mesenchymal stem cell transplantation procedure was well tolerated. Twelve patients completed the study. In 8 patients, improvements in Model for End-Stage Liver Disease (MELD) scores were observed. Serum albumin levels markedly increased in the third month. In patients with nonresponder hepatitis C, HCV RNA levels both became negative after mesenchymal stem cell transplantation. Histopathological examinations of liver tissues before and at 6 months after transplantation revealed no change in liver tissue regeneration or fibrosis. However, in 5 patients, hepatitis activity index scores decreased. Conclusion: Autologous mesenchymal stem cell transplantation via peripheral vein is safe and feasible. Consecutive liver biopsy examinations suggested that mesenchymal stem cells could not reach the liver in a sufficient amount. Improvement in patients and clearance of HCV RNA may have occurred through immunomodulatory mediators secreted by transplanted mesenchymal stem cells, namely the "endocrine" effect.

Investigation of regenerative and tiss ue-specific activity of tot al RNA of bone marrow cells

“…У крыс-доноров забирали костный мозг через 12 часов после резекции печени (указанный интервал, необходим для появления в костном мозге морфогенетически активных клеток) и получали из него мононуклеарную (гемопоэтическую) фракцию ККМ. Для выявления у этих клеток адресной (гепатоспецифической) индукционной активности выделенную фракцию донорских мононуклеарных ККМ вводили однократно внутрибрюшинно интактным (неоперированным) крысам-реципиентам (n = 27) либо в виде свежевыделенных активированных гепатэктомией мононуклеарных ККМ в дозе: 2,5×10 6 , или 5,0×10 6 , или 3,5×10 7 клеток на крысу (n = 12; группа 1) либо в виде общей (суммарной) РНК, предварительно полученной из таких же ККМ, в дозе 30 мкг/100 г веса животного (n = 10; группа 2). Контролем служили интактные крысы с введением 1,0 мл физиологического раствора (n = 5; группа 3).…”

“…Между тем механизмы, с помощью которых эти клетки осуществляют адресную доставку регенерационных сигналов в поврежденную ткань, остаются малоизученными. Показано, что выработка клетками костного мозга (ККМ) адресных регенерационных сигналов сопровождается появлением у этих клеток паракринных свойств [4][5][6][7][8], а это свидетельствует о происходящем репрограммировании их генома при запуске регенерационного процесса. Анализ возможных механизмов репрограммирования генома ККМ при восстановительных процессах позволил связать их с недавно открытым классом многочисленных регуляторных белок-некодирующих РНК в клетках, и прежде всего с молекулами микро-РНК (к настоящему времени выделено свыше 3000 различных микро-РНК) [9,10].…”

“…Materials and methods. By method of adoptive transfer in rats (n = 37) the mitotic and proliferative activity of liver and kidney cells were studied in intact recipients after intraperitoneal injection: the mononuclear BMCs -2,5×10 6 ; 5,0×10 6 ; 3,5×10 7 cells -group 1 and the total RNA of the same BMCs (30μg/100g of weight) -group 2 from donors in 12 hours after 70-75% of hepatectomy; in group 3 (control), a saline solution was injected. RNA from BMCs was extracted by the method developed by the «Evrogen» firm (Russia) with the reagent Extract RNA.…”

Stem Cell Therapies for Treatment of Liver Disease

“…Hepatitis C patients have also been treated with peripheral injection of autologous MSCs, with MELD score improvement but no change in liver fibrosis or regeneration on histopathological examination at six months post-treatment. HCV RNA levels became negative in patients with non-responder hepatitis C, suggesting that these cells have an immunomodulatory effect [115]. In a liver fibrosis rat model, adipose tissue-derived MSC infusion suppressed fibrosis progression and slightly ameliorated liver function.…”

Human Mesenchymal Stem Cell Transfusion for End Stage Liver Disease: A Case Series and Literature Review

“…In 8 of the patients, improvements in the Model for End-Stage Liver Disease (MELD) scores were observed. Serum albumin levels markedly increased in the third month[6]. Amer et al infused partially differentiated bone marrow derived MSCs into 20 subjects with HCV-induced cirrhosis via the intrasplenic or portal vein.…”