Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2021; 13(5): 452-469
Published online May 26, 2021. doi: 10.4252/wjsc.v13.i5.452
Disease modifying treatment of spinal cord injury with directly reprogrammed neural precursor cells in non-human primates
Vladimir P Baklaushev, Oleg V Durov, Vladimir A Kalsin, Eugene V Gulaev, Sergey V Kim, Ilya L Gubskiy, Veronika A Revkova, Ekaterina M Samoilova, Pavel A Melnikov, Dzhina D Karal-Ogly, Sergey V Orlov, Alexander V Troitskiy, Vladimir P Chekhonin, Alexander V Averyanov, Jan-Eric Ahlfors
Vladimir P Baklaushev, Vladimir A Kalsin, Veronika A Revkova, Ekaterina M Samoilova, Alexander V Averyanov, Biomedical Research, Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, FMBA of Russia, Moscow 115682, Moskva, Russia
Oleg V Durov, Eugene V Gulaev, Department of Neurosurgery, Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, FMBA, Moscow 115682, Moskva, Russia
Sergey V Kim, Department of Anesthesiology, N.N.Blokhin Russian Cancer Research Centre, Moscow 115478, Moskva, Russia
Ilya L Gubskiy, Ilya L Gubskiy, Radiology and Clinical Physiology Scientific Research Center, Federal center of brain research and neurotechnologies of the Federal Medical Biological Agency, Moscow 117997, Russia
Pavel A Melnikov, Department of Neurobiology, Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119992, Moskva, Russia
Dzhina D Karal-Ogly, Sergey V Orlov, Department of Primatology, Russian Acad Med Sci, Research Institute of Medical Primatology, Sochi 119992, Sochi, Russia
Alexander V Troitskiy, Department of Vascular Surgery, Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, FMBA of Russia, Moscow 115682, Moskva, Russia
Vladimir P Chekhonin, Department of Basic and Applied Neurobiology, V.P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Russia
Vladimir P Chekhonin, Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University (RNRMU), Moscow 115682, Moskva, Russia
Jan-Eric Ahlfors, New World Laboratories, Laval H7V 4A7, Quebec, Canada
Author contributions: Baklaushev VP and Ahlfors JE designed and coordinated the study and wrote the manuscript; Durov OV and Kim SV conducted the surgery; Kalsin VA, Revkova VA, and Samoilova EM propagated and characterized stem cells; Gulaev EV registered and interpreted evoked potentials; Gubskiy IL conducted magnetic resonance diffusion tensor imaging; Melnikov PA conducted confocal microscopy; Karal-Ogly DD and Orlov SV coordinated animal care; Troitskiy AV, Chekhonin VP, and Averyanov AV coordinated data analyses and revised the manuscript.
Supported by Russian Science Foundation, No. 16-15-10432
Institutional review board statement: The study was reviewed and approved by the Federal Research and Clinical Center Institutional Review Board (Approval from September 29, 2020).
Institutional animal care and use committee statement: The protocol of the study was approved by the Bioethics Committee of Research Institute of Medical Primatology (Statement from July 13th, 2016), and the Local Ethical Committee of the FRCC of FMBA of Russia (Statement No. 10b of September 12, 2016).
Conflict-of-interest statement: Authors declare no conflict of interests.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at baklaushev.vp@fnkc-fmba.ru.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Vladimir P Baklaushev, DSc, MD, PhD, Associate Professor, Biomedical Research, Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, FMBA of Russia, Orekhoviy BLVD, 28, Moscow 115682, Moskva, Russia. serpoff@gmail.com
Received: October 27, 2020
Peer-review started: October 27, 2020
First decision: December 21, 2020
Revised: January 20, 2021
Accepted: April 21, 2021
Article in press: April 21, 2021
Published online: May 26, 2021
Core Tip

Core Tip: Here, we describe a novel regenerative therapy of spinal cord injury by means of intraspinal transplantation of directly reprogrammed neural precursor cells (drNPCs). We showed that after transplantation of drNPC non-human primates demonstrated a significant recovery of the paralyzed hindlimb and recovery of somatosensory and motor evoked potential of injured pathways. Immunohistochemical analysis showed that drNPCs maintained multipotency in the transplanted spinal cord for at least 12 wk, migrating to areas of axon growth cones. Our data demonstrated that drNPCs transplantation was safe and contributed to improvement of spinal cord function after acute complete spinal cord injury in non-human primates.