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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Phase I study on the safety and preliminary efficacy of allogeneic mesenchymal stem cells in hypoxic-ischemic encephalopathy
Serdar Kabataş, Erdinç Civelek, Necati Kaplan, Eyüp Can Savrunlu, Gülseli Berivan Sezen, Mourat Chasan, Halil Can, Ali Genç, Yener Akyuva, Osman Boyalı, Furkan Diren, Erdal Karaoz
Serdar Kabataş, Erdinç Civelek, Eyüp Can Savrunlu, Gülseli Berivan Sezen, Mourat Chasan, Osman Boyalı, Furkan Diren, Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, İstanbul 34255, Turkey
Serdar Kabataş, Erdinç Civelek, Pediatric Allergy-Immunology, Marmara University, Institute of Health Sciences, İstanbul 34854, Turkey
Serdar Kabataş, Center for Stem Cell and Gene Therapy Research and Practice, University of Health Sciences, İstanbul 34255, Turkey
Necati Kaplan, Department of Neurosurgery, Istanbul Rumeli University, Çorlu Reyap Hospital, Tekirdağ 59860, Turkey
Halil Can, Department of Neurosurgery, İstanbul Biruni University, Faculty of Medicine, İstanbul 34010, Turkey
Halil Can, Department of Neurosurgery, İstanbul Medicine Hospital, İstanbul 34203, Turkey
Ali Genç, Department of Neurosurgery, İstanbul Asya Hospital, İstanbul 34250, Turkey
Yener Akyuva, Department of Neurosurgery, Mustafa Kemal University, Faculty of Medicine, Hatay 31060, Turkey
Erdal Karaoz, Center for Regenerative Medicine and Stem Cell Research and Manufacturing (LivMedCell), Liv Hospital, İstanbul 34340, Turkey
Erdal Karaoz, Department of Histology and Embryology, İstinye University, Faculty of Medicine, İstanbul 34010, Turkey
Erdal Karaoz, Center for Stem Cell and Tissue Engineering Research and Practice, İstinye University, İstanbul 34340, Turkey
Author contributions: Kabataş S, Karaöz E were responsible for the concept and design; Kabataş S, Civelek E and Karaöz E in charge of supervision; Kabataş S, Civelek E, Kaplan N, Savrunlu EC, Sezen GB, Chasan M, Can H, Genç A, Akyuva Y, Boyalı O and Diren F accomplished analysis and/or interpretation; Kabataş S, Civelek E, Sezen GB, Chasan M, Can H, Genç A, Akyuva Y, Boyalı O, Diren F and Karaöz E were responsible for literature searching; Kabataş S, Kaplan N, Savrunlu EC and Karaöz E were responsible for writing manuscripts; Kabatas K, Civelek E, Kaplan N, Savrunlu EC and Karaöz E were responsible for critical reviews.
Institutional review board statement: Approval for the trial was obtained from the Turkish Ministry of Health, General Directorate of Health Services, Department of Organ/Tissue Transplantation and Dialysis Services, and the Scientific Committee (No. 56733164-203-E.2569).
Conflict-of-interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/ Corresponding author: Serdar Kabataş, MD, PhD, Chairman, Full Professor, Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, Serdar Kabataş, Karayolları Mahallesi, Osmanbey Caddesi 616, İstanbul 34255, Turkey. kabatasserdar@gmail.com
Received: December 24, 2020
Peer-review started: December 24, 2020
First decision: January 18, 2021
Revised: February 19, 2021
Accepted: March 12, 2021
Article in press: March 12, 2021
Published online: March 20, 2021
ARTICLE HIGHLIGHTS
Research background
To date, hypoxic ischemic encephalopathy (HIE) is refractory, including after cardiopulmonary resuscitation, hemorrhagic shock and cerebral infarction etc.
Research motivation
Limited treatment options exist for patients with HIE and substantial functional deficits. Thus, further clinical research investigations on this subject could be valuable.
Research objectives
The current study examined safety and preliminary efficacy estimates of allogeneic mesenchymal stem cells (MSCs) in this population.
Research methods
Entry criteria included HIE ≥ 6 mo prior, substantial impairment and disability. Enrollees received intrathecal, intramuscular, and intravenous administrations of Wharton’s jelly–derived MSCs at a target dose of 1 × 106/kg for each application route (twice a month for 2 mo).
Research results
Treatment was safe based on serial neurological and functional exams, laboratory tests, electroencephalographies, and magnetic resonance imaging.
Research conclusions
Therapeutic administration of stem cells has a theoretical role in the treatment of HIE. Although promising results from many publications have been reported, there is still no consensus on which cellular therapy should be administered to which patient at what time after HIE. There seems to be a need for a tremendous amount of work to elucidate the underlying mechanisms of how MSCs interact with damaged host tissues and how this interaction results in a cascade of events that lead to some functional neuronal recovery.
Research perspectives
These findings suggest that quality of the cells, optimization of the cell dose, standardization of the cell processing, the timing, route of administration and patient selection as well as the role of clinical experience of the physcisian are critical to the success of stem cell therapy in HIE patients.
