A pilot study of autologous CD34-depleted bone marrow mononuclear cell transplantation via the hepatic artery in five patients with liver failure |
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| Authors: | Chung-Hwa Park Si Hyun Bae Hee Yeon Kim Ja Kyung Kim Eun Sun Jung Ho Jong Chun Myeong Jun Song Sung-Eun Lee Seok Goo Cho Jong Wook Lee Jong Young Choi Seung Kew Yoon Nam Ik Han Young Sok Lee |
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| Affiliation: | 1. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea;2. Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea;3. Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul, Korea;4. Department of Catholic High Performance Cell Therapy Center, College of Medicine, The Catholic University of Korea, Seoul, Korea;5. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea;1. Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea;2. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea;3. Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea;4. Department of Medical Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea;1. Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;2. Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Graduate Institute of Clinical Medical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;3. Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;4. Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;5. Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;1. Department of Diagnostic Radiology, Interventional Radiology Section, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1471 Houston, TX 77030;2. Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1471 Houston, TX 77030;3. Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1471 Houston, TX 77030;4. Department of Radiology, Division of Interventional Radiology, New York–Presbyterian Hospital/Weill Cornell Medical Center, New York, New York |
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| Abstract: | Background aimsMany rodent experiments and human studies on stem cell therapy have shown promising therapeutic approaches to liver diseases. We investigated the clinical outcomes of five patients with liver failure of various causes who received autologous CD34-depleted bone marrow-derived mononuclear cell (BM-MNC) transplantation, including mesenchymal stromal cells, through the hepatic artery.MethodsCD34-depleted BM-MNCs were obtained from five patients waiting for liver transplantation by bone marrow aspiration and using the CliniMACS CD34 Reagent System (Miltenyi Biotech, Bergisch Gladbach, Germany), and autologous hepatic artery infusion was performed. The causes of hepatic decompensation were hepatitis B virus (HBV), hepatitis C virus (HCV), propylthiouracil-induced toxic hepatitis and Wilson disease.ResultsSerum albumin levels improved 1 week after transplantation from 2.8 g/dL, 2.4 g/dL, 2.7 g/dL and 1.9 g/dL to 3.3 g/dL, 3.1 g/dL, 2.8 g/dL and 2.6 g/dL. Transient liver elastography data showed some change from 65 kPa, 33 kPa, 34.8 kPa and undetectable to 46.4 kPa, 19.8 kPa, 29.1 kPa and 67.8 kPa at 4 weeks after transplantation in a patient with Wilson disease, a patient with HCV, and two patients with HBV. Ascites decreased in two patients. One of the patients with HBV underwent liver transplantation 4 months after the infusion, and the hepatic progenitor markers (cytokeratin CD]-7, CD-8, CD-9, CD-18, CD-19, c-Kit and epithelial cell adhesion molecule EpCAM]) were highly expressed in the explanted liver.ConclusionsSerum albumin levels, liver stiffness, liver volume, subjective healthiness and quality of life improved in the study patients. Although these findings were observed in a small population, the results may suggest a promising future for autologous CD34-depleted BM-MNC transplantation as a bridge to liver transplantation in patients with liver failure. |
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| Keywords: | autologous transplantation liver cirrhosis liver failure mesenchymal stromal cell |
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