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Effective Treatment of Severe Steroid-Resistant Acute Graft-Versus-Host Disease With Umbilical Cord-Derived Mesenchymal Stem Cells

Wu, Kang-Hsi1,2; Chan, Chin-Kan3,4; Tsai, Chris5; Chang, Yu-Hsiang6; Sieber, Martin5; Chiu, Tsan-Hung7; Ho, Ming7; Peng, Ching-Tien1,8,12; Wu, Han-Ping9,10; Huang, Jing-Long11,12

doi: 10.1097/TP.0b013e31821aba18
Clinical and Translational Research

Background. Severe steroid-resistant acute graft-versus-host disease (aGVHD) is associated with high mortality. Bone marrow-derived mesenchymal stem cells (BMMSC) have been found to be immunosuppressive, and intravenous infusion of BMMSC is an effective therapy for steroid-resistant aGVHD. However, acquiring BMMSC requires an invasive procedure.

Methods. We compared umbilical cord-derived mesenchymal stem cells (UCMSC) and BMMSC for morphology, surface markers expression, differentiation, proliferative potential, and their suppressive effects on peripheral blood mononuclear cell proliferation. After institutional review board approved, we intravenously infused ex vivo expanded third-party UCMSC into two patients with severe steroid-resistant aGVHD. Adverse effects and patient responses of UCMSC were monitored. All procedures for UCMSC processing complied with current good tissue practice requirements.

Results. We found that UCMSC had superior proliferative potential and more suppressive effects on peripheral blood mononuclear cell proliferation compared with BMMSC. The aGVHD improved dramatically after each of four infusions of UCMSC into the two patients. No adverse effects were noted. Both patients are doing well now.

Conclusions. Considering that acquiring UCMSC is noninvasive, these cells would appear to be the ideal candidates for clinical cell-based therapies. This is the first report of UCMSC in a human clinical application, and this procedure seems both feasible and safe. These findings suggested that UCMSC were effective for treating aGVHD.

1 Department of Pediatrics, Children's Hospital and School of Chinese Medicine, China Medical University Hospitals, Taichung, Taiwan.

2 Stem Cell Research Laboratory, Department of Medical Research, China Medical, University Hospital, Taichung, Taiwan.

3 Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan.

4 Department of Pediatrics, Taoyuan General Hospital, Taoyuan, Taiwan.

5 Bionet Corp, Taipei, Taiwan.

6 Department of Pediatrics, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan.

7 Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.

8 Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan.

9 Department of Pediatrics, Buddhist Tzu-Chi General Hospital, Taichung Branch, Taichung, Taiwan.

10 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

11 Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

This work was supported by the Ministry of Economic Affairs of Taiwan; in part by the Taoyuan General Hospital Project grants PTH9702 and North 98017 and the China Medical University Hospital grant DMR-96-001.

12 Address correspondence to: Ching-Tien Peng, M.D., Department of Pediatrics, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan; or Jing-Long Huang, M.D., Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, No. 5, Fu-Hsin Street, Kweishan, Taoyuan, Taiwan.

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Chin-Kan Chan contributed equally to this work.

K.H.W. and C.K.C. participated in research design; H.P.W. and C.T.P. participated in the writing of the manuscript; C.T., Y.H.C., M.S., T.H.C., M.H., and J.L.H. participated in the performance of the research.

Received 25 October 2010. Revision requested 15 November 2010.

Accepted 15 March 2011.

© 2011 Lippincott Williams & Wilkins, Inc.