Oncotarget

Research Papers:

Investigated the safety of intra-renal arterial transfusion of autologous CD34+ cells and time courses of creatinine levels, endothelial dysfunction biomarkers and micro-RNAs in chronic kidney disease patients-phase I clinical trial

Mel S. Lee, Fan-Yen Lee, Yung-Lung Chen, Pei-Hsun Sung, Hsin-Ju Chiang, Kuan-Hung Chen, Tien-Hung Huang, Yi-Ling Chen, John Y. Chiang, Tsung-Cheng Yin, Hsueh-Wen Chang and Hon-Kan Yip _

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Oncotarget. 2017; 8:17750-17762. https://doi.org/10.18632/oncotarget.14831

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Abstract

Mel S. Lee1,*, Fan-Yen Lee2,*, Yung-Lung Chen3, Pei-Hsun Sung3, Hsin-Ju Chiang4, Kuan-Hung Chen5, Tien-Hung Huang3, Yi-Ling Chen3, John Y. Chiang6,7, Tsung-Cheng Yin1, Hsueh-Wen Chang8, Hon-Kan Yip3,9,10,11,12

1Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

3Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

4Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

5Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

6Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan

7Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, Taiwan

8Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

9Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

10Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

11Department of Nursing, Asia University, Taichung, Taiwan

12Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

*These authors contributed equaly to this work

Correspondence to:

Hon-Kan Yip, email: han.gung@msa.hinet.net

Keywords: chronic kidney disease, endothelial dysfunction, endothelial progenitor cells, autologous transfusion of CD34+ cells into renal artery

Received: September 13, 2016     Accepted: January 07, 2017     Published: January 27, 2017

ABSTRACT

This was a phase I clinical trial to investigate the safety of autologous peripheral-blood-derived CD34+ cell therapy for patients with chronic kidney disease (CKD-treatment) (i.e., at Stages III and IV). Between November 2014 and October 2015, a total of 10 study patients were prospectively enrolled into this phase I trial. Patients who failed to enroll into the trial in the initial state of eligibility assessment were served as CKD-control group (n = 9). The health-control group was composed of 10 volunteers for the purposes of comparing (1) circulation level of endothelial progenitor cells (EPCs), (2) angiogenesis ability, and (3) anti-apoptotic miRNAs between healthy subjects and CKD patients. CD34+ cells (5.0 x 107) were transfused into right-renal artery after subcutaneous G-CSF injection (5μg/kg/twice a day for 4 days). Circulating EPC number, angiogenesis capacity (i.e., Matrigel assay) and anti-apoptotic miRNAs (miR-374a-5p/miR-19a-3p/ miR-106b-5p/miR-26b-5p/ miR-20a-5p) were significantly lower in CKD patients than in healthy subjects (all p < 0.001). Flow-cytometric analysis of renal-vein blood samplings (i.e., at 0/5/10/30 mins after cell transfusion) showed the EPC level was significantly progressively increased (p < 0.001). Procedural safety was 100% with all patients uneventfully discharged and one-year survival rate was 100%. The paired-t test showed serum creatinine maintained the same level between the baseline and at the end of one-year follow-up (all p > 0.4), whereas the net increase between initial and final creatinine level was higher in CKD-control than in CKD-treatment. In conclusion, CD34+ cell therapy was safe and maintained the renal function in stationary state at the end of study period.


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