PMID- 30294904 OWN - NLM STAT- MEDLINE DCOM- 20200911 LR - 20210109 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 25 IP - 4 DP - 2019 Apr TI - Bone marrow mesenchymal stem cells stimulated with low-intensity pulsed ultrasound: Better choice of transplantation treatment for spinal cord injury: Treatment for SCI by LIPUS-BMSCs transplantation. PG - 496-508 LID - 10.1111/cns.13071 [doi] AB - Stem cell transplantation, especially treatment with bone marrow mesenchymal stem cells (BMSCs), has been considered a promising therapy for the locomotor and neurological recovery of spinal cord injury (SCI) patients. However, the clinical benefits of BMSCs transplantation remain limited because of the considerably low viability and inhibitory microenvironment. In our research, low-intensity pulsed ultrasound (LIPUS), which has been widely applied to clinical applications and fundamental research, was employed to improve the properties of BMSCs. The most suitable intensity of LIPUS stimulation was determined. Furthermore, the optimized BMSCs were transplanted into the epicenter of injured spinal cord in rats, which were randomized into four groups: (a) Sham group (n = 10), rats received laminectomy only and the spinal cord remained intact. (b) Injury group (n = 10), rats with contused spinal cord subjected to the microinjection of PBS solution. (c) BMSCs transplantation group (n = 10), rats with contused spinal cord were injected with BMSCs without any priming. (d) LIPUS-BMSCs transplantation group (n = 10), BMSCs stimulated with LIPUS were injected at the injured epicenter after contusion. Rats were then subjected to behavioral tests, immunohistochemistry, and histological observation. It was found that BMSCs stimulated with LIPUS obtained higher cell viability, migration, and neurotrophic factors expression in vitro. The rate of apoptosis remained constant. After transplantation of BMSCs and LIPUS-BMSCs postinjury, locomotor function was significantly improved in LIPUS-BMSCs transplantation group with higher level of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the epicenter, and the expression of neurotrophic receptor was also enhanced. Histological observation demonstrated reduced cavity formation in LIPUS-BMSCs transplantation group when comparing with other groups. The results suggested LIPUS can improve BMSCs viability and neurotrophic factors expression in vitro, and transplantation of LIPUS-BMSCs could promote better functional recovery, indicating possible clinical application for the treatment of SCI. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Ning, Guang-Zhi AU - Ning GZ AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Song, Wen-Ye AU - Song WY AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Xu, Hong AU - Xu H AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. AD - Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, China. FAU - Zhu, Ru-Sen AU - Zhu RS AD - Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, China. FAU - Wu, Qiu-Li AU - Wu QL AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Wu, Yu AU - Wu Y AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Zhu, Shi-Bo AU - Zhu SB AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Li, Ji-Qing AU - Li JQ AD - Department of Electronic Engineering, Tianjin University of Science and Technology, Tianjin, China. FAU - Wang, Man AU - Wang M AD - Department of Electronic Engineering, Tianjin University of Science and Technology, Tianjin, China. FAU - Qu, Zhi-Gang AU - Qu ZG AD - Department of Electronic Engineering, Tianjin University of Science and Technology, Tianjin, China. FAU - Feng, Shi-Qing AU - Feng SQ AUID- ORCID: 0000-0001-9437-7674 AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181008 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 SB - IM MH - Animals MH - Bone Marrow Transplantation/*methods MH - Cells, Cultured MH - Female MH - Mesenchymal Stem Cell Transplantation/*methods MH - Random Allocation MH - Rats MH - Rats, Wistar MH - Spinal Cord Injuries/physiopathology/*therapy MH - Treatment Outcome MH - Ultrasonic Therapy/*methods MH - *Ultrasonic Waves PMC - PMC6488928 OTO - NOTNLM OT - bone marrow mesenchymal stem cells OT - low-intensity pulsed ultrasound OT - spinal cord injury OT - stem cell transplantation COIS- The authors declare no conflict of interest. EDAT- 2018/10/09 06:00 MHDA- 2020/09/12 06:00 PMCR- 2018/10/08 CRDT- 2018/10/09 06:00 PHST- 2018/03/28 00:00 [received] PHST- 2018/09/04 00:00 [revised] PHST- 2018/09/07 00:00 [accepted] PHST- 2018/10/09 06:00 [pubmed] PHST- 2020/09/12 06:00 [medline] PHST- 2018/10/09 06:00 [entrez] PHST- 2018/10/08 00:00 [pmc-release] AID - CNS13071 [pii] AID - 10.1111/cns.13071 [doi] PST - ppublish SO - CNS Neurosci Ther. 2019 Apr;25(4):496-508. doi: 10.1111/cns.13071. Epub 2018 Oct 8.