Intraportal Infusion of Bone Marrow Mononuclear or CD133+ Cells in Patients With Decompensated Cirrhosis: A Double‐Blind Randomized Controlled Trial

• Published in: Stem cells translational medicine Vol. 5; no. 1; pp. 87 - 94
• Main Authors: Mohamadnejad, Mehdi, Vosough, Massoud, Moossavi, Shirin, Nikfam, Sepideh, Mardpour, Soura, Akhlaghpoor, Shahram, Ashrafi, Mandana, Azimian, Vajiheh, Jarughi, Neda, Hosseini, Seyedeh-Esmat, Moeininia, Fatemeh, Bagheri, Mohamad, Sharafkhah, Maryam, Aghdami, Nasser, Malekzadeh, Reza, Baharvand, Hossein
• Format: Journal Article
• Language: English
• Published: Durham, NC, USA AlphaMed Press 01-01-2016; Oxford University Press
• Subjects: AC133 Antigen; Administrative support; Adult; Aged; Antigens, CD; Autografts; Bias; Bone marrow; Bone Marrow Transplantation; Cell-based therapy; Cirrhosis; Data analysis; Double-Blind Method; Double-blind studies; End Stage Liver Disease - pathology; End Stage Liver Disease - physiopathology; End Stage Liver Disease - therapy; Esophagus; Fibrosis - pathology; Fibrosis - physiopathology; Fibrosis - therapy; Glycoproteins; Hematopoietic stem cell; Hepatitis; Hepatocellular carcinoma; Hepatocytes; Humans; Hypertension; Leukocyte Transfusion; Leukocytes (mononuclear); Leukocytes, Mononuclear - transplantation; Liver cirrhosis; Liver diseases; Liver transplantation; Male; Middle Aged; Patients; Peptides; Regenerative medicine; Research centers; Stem cells; Studies; Tissue Engineering and Regenerative Medicine; Transplants & implants; Ultrasonic imaging; Iran; Cirrhosis; Cell-based therapy; Hematopoietic stem cell; Regenerative medicine
• ISSN: 2157-6564; 2157-6580
• DOI: 10.5966/sctm.2015-0004

The present study assessed the effects of intraportal infusions of autologous bone marrow‐derived mononuclear cells (MNCs) and/or CD133+ cells on liver function in patients with decompensated cirrhosis. We randomly assigned 27 eligible patients to a placebo, MNCs, and/or CD133+ cells. Cell infusions were performed at baseline and month 3. We considered the absolute changes in the Model for End‐Stage Liver Disease (MELD) scores at months 3 and 6 after infusion as the primary outcome. The participants and those who assessed the outcomes were unaware of the treatment intervention assignments. After 6 months, 9 patients were excluded because of liver transplantation (n = 3), hepatocellular carcinoma (n = 1), loss to follow‐up (n = 3), and death (n = 2). The final analysis included 4 patients from the CD133+ group, 8 from the MNC group, and 6 from the placebo group. No improvement was seen in the MELD score at month 6 using either CD133+ cells or MNC infusions compared with placebo. However, at month 3 after infusion, a trend was seen toward a higher mean absolute change in the MELD score in patients who had received CD133+ cells compared with placebo (−2.00 ± 1.87 vs. −0.13 ± 1.46; p = .08). No significant adverse events occurred in the present study. A transient improvement in the MELD score was observed in subjects treated with CD133+ cells but not in the MNC or placebo group. Although the study was not powered to make definitive conclusions, the data justify further study of CD133+ therapy in cirrhotic patients.
Significance
Cell therapy is a new approach in liver disease. Several clinical experiments have been reported on the safety of bone marrow‐derived stem cells to treat liver disorders. However, the effectiveness of these approaches in the long‐term follow‐ups of patients initiated controversial discussions among the scientific community. A double‐blind randomized controlled trial was designed to address this concern scientifically. A transient improvement in the patients' signs occurred; however, for a sustainable result, more work is needed. The results of multiple administrations of cells reported in the present study can be compared with the results from other single‐injection studies.
The present study assessed the effects of intraportal infusions of autologous bone marrow‐derived mononuclear cells (MNCs) and/or CD133+ cells on liver function in patients with decompensated cirrhosis in a double‐blind randomized controlled trial. No significant adverse events occurred in the present study. A transient improvement in the Model for End‐Stage Liver Disease score was observed in subjects treated with CD133+ cells but not in the MNC or placebo group. Although the study was not powered to make definitive conclusions, the data justify further study of CD133+ therapy in cirrhotic patients.