A pilot study of autologous CD34-depleted bone marrow mononuclear cell transplantation via the hepatic artery in five patients with liver failure

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Background aims: Many 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. Methods: CD34-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. Results: Serum 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. Conclusions: Serum 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.

Original languageEnglish
Pages (from-to)1571-1579
Number of pages9
JournalCytotherapy
Volume15
Issue number12
DOIs
StatePublished - Dec 2013

Bibliographical note

Funding Information:
This study was supported partly by a grant from the Korea Health Technology R & D Project (A084950), Ministry of Health & Welfare, Republic of Korea, partly by Seoul St. Mary's Clinical Medicine Research Program, The Catholic University of Korea and partly by a grant from Catholic Institute of Cell Therapy, The Catholic University of Korea.

Keywords

  • Autologous transplantation
  • Liver cirrhosis
  • Liver failure
  • Mesenchymal stromal cell

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