Randomized Controlled Trial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2017; 9(8): 133-143
Published online Aug 26, 2017. doi: 10.4252/wjsc.v9.i8.133
Phase I/II randomized controlled trial of autologous bone marrow-derived mesenchymal stem cell therapy for chronic stroke
Kam Sze Tsang, Chi Ping Stephanie Ng, Xian Lun Zhu, George Kwok Chu Wong, Gang Lu, Anil Tejbhan Ahuja, Ka Sing Lawrence Wong, Ho Keung Ng, Wai Sang Poon
Kam Sze Tsang, Chi Ping Stephanie Ng, Xian Lun Zhu, George Kwok Chu Wong, Gang Lu, Wai Sang Poon, Department of Surgery, the Chinese University of Hong Kong, Hong Kong, China
Kam Sze Tsang, Ho Keung Ng, Department of Anatomical and Cellular Pathology, the Chinese University of Hong Kong, Hong Kong, China
Anil Tejbhan Ahuja, Department of Imaging and Interventional Radiology, the Chinese University of Hong Kong, Hong Kong, China
Ka Sing Lawrence Wong, Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong, China
Author contributions: Tsang KS conducted experiments, analyzed data and wrote the manuscript; Ng CPS coordinated the trial and performed statistical analysis of data; Zhu XL and Wong GKC consulted and administered cells and placebos to patients; Lu G reviewed data; Ahuja AT analyzed radio-imaging; Wong KSL and Ng HK contributed intellectual content; Poon WS designed, supervised and monitored the trial, secured grant support, interpreted data and revised the manuscript.
Institutional review board statement: The randomized, controlled, double-blind, phase I/II clinical trial was approved by the Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee of Hong Kong Hospital Authority in accordance with the principles of the Declaration of Helsinki and International Conference on Harmonisation - Good Clinical Practice.
Clinical trial registration statement: The clinical trial CREC #2006.425-T was registered at http://crec.cuhk.edu.hk.
Informed consent statement: Written informed consent was obtained from all subjects - in the case of vegetative state, from their next of kin.
Conflict-of-interest statement: All authors declared that no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wai Sang Poon, MD, Division of Neurosurgery, Department of Surgery, the Chinese University of Hong Kong, Prince of Wales Hospital, 30-32, Ngan Shing Road, Shatin, Hong Kong, China. wpoon@cuhk.edu.hk
Telephone: +852-26322624 Fax: +852-26327974
Received: February 11, 2017
Peer-review started: February 15, 2017
First decision: March 8, 2017
Revised: June 27, 2017
Accepted: July 14, 2017
Article in press: July 17, 2017
Published online: August 26, 2017
Processing time: 193 Days and 19.1 Hours
Abstract
AIM

To examine the safety and efficacy of mesenchymal stem cell (MSC) therapy for intracerebral haemorrhage with neurological dysfunctions for a year.

METHODS

MSC were ex vivo expanded from 29 mL (17-42 mL) autologous bone marrow. Patients were randomized to have two intravenous injections of autologous MSC or placebos in four weeks apart. Neurological functions and clinical outcomes were monitored before treatment and at 12th, 16th, 24th, 36th and 60th week upon completion of the treatment.

RESULTS

A mean of 4.57 × 107 (range: 1.43 × 107-8.40 × 107) MSC per infusion was administered accounting to 8.54 × 105 (2.65 × 105-1.45 × 106) per kilogram body weight in two occasions. There was neither adverse event at time of administration nor sign of de novo tumour development among patients after monitoring for a year post MSC therapy. Neuro-restoration and clinical improvement in terms of modified Barthel index, functional independence measure and extended Glasgow Outcome Scale were evident among patients having MSC therapy compared to patients receiving placebos.

CONCLUSION

Intravenous administration of autologous bone marrow-derived MSC is safe and has the potential of improving neurological functions in chronic stroke patients with severe disability.

Keywords: Stroke; Intracerebral haemorrhage; Central nervous system; Mesenchymal stem cells; Cell therapy

Core tip: Contemporary treatments are ineffective in restoring lost neurological functions after stroke. Many stroke patients were noted to have lesions close to the sub-ventricular zone. The likely beneficial effects of mesenchymal stem cell (MSC) treatment might correlate with the spatial lesion, not part of the sub-ventricular zone where endogenous neurogenesis persists during adulthood, and indirect chaperon effects of MSC promote endogenous neuro-regeneration. We administered MSC intravenously to patients having severe neurological disability and presenting stable baseline scores one year after the onset of intracerebral haemorrhage to eliminate confounding attributes to the observation of MSC-mediated neurological recovery.