title: Intraportal Infusion of Bone Marrow Mononuclear or CD133+ Cells in Patients With Decompensated Cirrhosis: A Double-Blind Randomized Controlled Trial.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mohamadnejad
authors.affiliation: Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran.
authors.forename: Massoud
authors.initials: M
authors.lastname: Vosough
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Moossavi
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Nikfam
authors.affiliation: Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran.
authors.forename: Soura
authors.initials: S
authors.lastname: Mardpour
authors.affiliation: Noor Medical Imaging Center, Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Akhlaghpoor
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mandana
authors.initials: M
authors.lastname: Ashrafi
authors.affiliation: Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran.
authors.forename: Vajiheh
authors.initials: V
authors.lastname: Azimian
authors.affiliation: Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran.
authors.forename: Neda
authors.initials: N
authors.lastname: Jarughi
authors.affiliation: Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran.
authors.forename: Seyedeh-Esmat
authors.initials: SE
authors.lastname: Hosseini
authors.affiliation: Department of Internal Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Moeininia
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Bagheri
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Sharafkhah
authors.affiliation: Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran.
authors.forename: Nasser
authors.initials: N
authors.lastname: Aghdami
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Baharvand@RoyanInstitute.org malek@tums.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
authors.affiliation: Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran Baharvand@RoyanInstitute.org malek@tums.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D064592:Autografts; D016026:Bone Marrow Transplantation; D004311:Double-Blind Method; D058625:End Stage Liver Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D005355:Fibrosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006023:Glycoproteins; D006801:Humans; D017708:Leukocyte Transfusion; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D010455:Peptides
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides
keywords: Cell-based therapy; Cirrhosis; Hematopoietic stem cell; Regenerative medicine