Autologous Bone Marrow Stem Cell Transplantation in Liver Cirrhosis after Correcting Nutritional Anomalies, A Controlled Clinical Study


Abbas Esmaeilzadeh, M.D, 1,#Homeira Ommati, M.D, 1,#Mohammad Mahdi Kooshyar, M.D, 2Lida Jarahi, M.D, 3Kambiz Akhavan Rezayat, M.D, 1Samaneh Saberi, M.Sc, 4Massoud Vosough, M.D., Ph.D, 5,6,*Ali Ghassemi, M.D, 7,*
Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Gastroenterology and Hepatology Research Center, Mashhad, Iran
Department of Hematology and Oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Community Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
HPGC Group, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Pediatric Hematology and Oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Gastroenterology and Hepatology Research Center, Mashhad, Iran
Department of Hematology and Oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Community Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
HPGC Group, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Pediatric Hematology and Oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
*Corresponding Address: P.O.Box: 16635-148 Department of Regenerative Medicine Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran P.O.Box: 9177899191 Department of Pediatric Hematology and Oncology Faculty of Medicine Mashhad University of Medical Sciences Mashhad Iran Emails:masvos@royaninstitute.org,Ghasemial@mums.ac.ir

The first three authors equally contributed to this work.

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Esmaeilzadeh Abbas, Ommati Homeira, Kooshyar Mohammad Mahdi, Jarahi Lida, Akhavan Rezayat Kambiz, Saberi Samaneh, Vosough Massoud, Ghassemi Ali. Autologous Bone Marrow Stem Cell Transplantation in Liver Cirrhosis after Correcting Nutritional Anomalies, A Controlled Clinical Study . Cell J. 2019; 21(3): 268-272.

Abstract

Objective

Liver transplantation is the gold standard approach for decompensated liver cirrhosis. In recent years, stem cell therapy has raised hopes that adjusting some clinical and laboratory parameters could lead to successful treatments for this disease. Cirrhotic patients may have multiple systemic abnormalities in peripheral blood and irregular cell populations in bone marrow (BM). Correcting these abnormalities before BM aspiration may improve the effectiveness of cell-based therapy of liver cirrhosis.

Materials and Methods

In this controlled clinical trial study, 20 patients with decompensated liver cirrhosis were enrolled. Patients were randomly assigned to control and experimental groups. Blood samples were obtained to measure vitamin B12, folate, serum iron, total iron bonding capacity (TIBC) and ferritin before any intervention. Furthermore, the iron storage and fibrosis level in BM biopsies, as well as the percentage of different cell populations, were evaluated. Prior to cell isolation for transplantation, we performed palliative supplement therapy followed by a correction of nutritional deficiencies. Mononuclear cells (MNCs) were then isolated from BM aspirates and transfused through peripheral vein in patients in the experimental group. The model of end-stage liver disease (MELD) score, The international normalized ratio (INR), serum albumin and bilirubin levels were assessed at 0 (baseline), 3 and 6 months after cell transplantation.

Results

The MELD score (P=0.0001), INR (P=0.012), bilirubin (P<0.0001) and total albumin (P<0.0001) levels improved significantly in the experimental group after cell transplantation compared to the baseline and control groups. Moreover, the increase in serum albumin levels of patients in the experimental group was statistically significant 6 months after transplantation.

Conclusion

We have successfully improved the conditions of preparing -BM-derived stem cells for transplantation. Although these cells are relatively safe and have been shown to improve some clinical signs and symptoms temporarily, there need to be more basic studies regarding the preparation steps for effective clinical use (Registration number: IRCT2014091919217N1).