Olig2-expressing Mesenchymal Stem Cells Enhance Functional Recovery after Contusive Spinal Cord Injury
Hwan-Woo Park1,2,*, Soonyi Oh1,*, Kyung Hee Lee3, Bae Hwan Lee4, Mi-Sook Chang1,5
1Laboratory of Stem Cell & Neurobiology, Department of Oral Anatomy, Dental Research Institute & School of Dentistry, Seoul National University, Seoul, Korea, 2Department of Cell Biology, Myunggok Medical Research Institute, Konyang University College of Medicine, Daejeon, Korea, 3Department of Dental Hygiene, Dongseo University, Busan, Korea, 4Department of Physiology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea, 5Neuroscience Research Institute, Seoul National University, Seoul, Korea
Correspondence to: Mi-Sook Chang
Laboratory of Stem Cell & Neurobiology, Department of Oral Anatomy, Dental Research Institute & School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
Tel: +82-2-740-8628, Fax: +82-2-745-1906
E-mail: mschang@snu.ac.kr
*These authors contributed equally to this work.
Laboratory of Stem Cell & Neurobiology, Department of Oral Anatomy, Dental Research Institute & School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
Tel: +82-2-740-8628, Fax: +82-2-745-1906
E-mail: mschang@snu.ac.kr
*These authors contributed equally to this work.
Received August 25, 2018; Revised October 3, 2018; Accepted October 3, 2018.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Abstract
- Background and Objectives: Glial scarring and inflammation after spinal cord injury (SCI) interfere with neural regeneration and functional recovery due to the inhibitory microenvironment of the injured spinal cord. Stem cell transplantation can improve functional recovery in experimental models of SCI, but many obstacles to clinical application remain due to concerns regarding the effectiveness and safety of stem cell transplantation for SCI patients. In this study, we investigated the effects of transplantation of human mesenchymal stem cells (hMSCs) that were genetically modified to express Olig2 in a rat model of SCI.
Methods: Bone marrow-derived hMSCs were genetically modified to express Olig2 and transplanted one week after the induction of contusive SCI in a rat model. Spinal cords were harvested 7 weeks after transplantation.
Results: Transplantation of Olig2-expressing hMSCs significantly improved functional recovery in a rat model of contusive SCI model compared to the control hMSC-transplanted group. Transplantation of Olig2-expressing hMSCs also attenuated glial scar formation in spinal cord lesions. Immunohistochemical analysis showed that transplanted Olig2-expressing hMSCs were partially differentiated into Olig1-positive oligodendrocyte-like cells in spinal cords. Furthermore, NF-M-positive axons were more abundant in the Olig2-expressing hMSC-transplanted group than in the control hMSC-transplanted group.
Conclusions: We suggest that Olig2-expressing hMSCs are a safe and optimal cell source for treating SCI. - Keywords : Olig2, Mesenchymal stem cells, Spinal cord injury, Transplantation
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