Synergic Effect of Combined Therapy of Hyperbaric Oxygen and Adipose-Derived Mesenchymal Stem Cells on Improving Locomotor Recovery After Acute Traumatic Spinal Cord Injury in Rat Mainly Through Downregulating Inflammatory and Cell-Stress Signalings

Author:

Yin Tsung-Cheng12,Shao Pei-Lin3,Chen Kuan-Hung4,Lin Kun-Chen4,Chiang John Y.56,Sung Pei-Hsun789,Wu Shun-Cheng101112,Li Yi-Chen6131415,Yip Hon-Kan267816ORCID,Lee Mel S.1

Affiliation:

1. Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, Taiwan

2. Center for General Education, Cheng Shiu University, Kaohsiung, Taiwan

3. Department of Nursing, Asia University, Taichung, Taiwan

4. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, Taiwan

5. Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan

6. Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, Taiwan

7. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, Taiwan

8. Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung, Taiwan

9. Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung, Taiwan

10. Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan

11. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan

12. Post-Baccalaureate Program in Nursing, Asia University, Taichung, Taiwan

13. Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

14. Center of Cell Therapy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

15. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

16. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

Abstract

This study tested whether combined hyperbaric oxygen (HBO) and allogenic adipose-derived mesenchymal stem cells (ADMSCs) would be superior to either one for improving the locomotor recovery in rat after acute traumatic spinal cord injury (TSCI) in rat. Adult-male Sprague–Dawley rats were equally categorized into group 1 (sham-operated control), group 2 (TSCI), group 3 (TSCI + HBO for 1.5 h/day for 14 consecutive days after TSCI), group 4 (TSCI + ADMSCs/1.2 × 106 cells by intravenous injection at 3 h and days 1/2 after TSCI), and group 5 (TSCI + HBO + ADMSCs), euthanized, and spinal cord tissue was harvested by day 49 after TSCI. The protein expressions of oxidative-stress (NOX-1/NOX-2), inflammatory-signaling (TLR-4/MyD88/IL-1β/TNF-α/substance-p), cell-stress signaling (PI3K/p-AKT/p-mTOR), and the voltage-gated sodium channel (Nav1.3/1.8/1.9) biomarkers were highest in group 2, lowest in group 1, and significantly lower in group 5 than in groups 3/4 (all P <0.0001), but they did not differ between groups 3 and 4. The spinal cord damaged area, the cellular levels of inflammatory/DNA-damaged biomarkers (CD68+/GFAP+/γ-H2AX+ cells), mitogen-activated protein kinase family biomarkers (p-P38/p-JNK/p-ERK1/2), and cellular expressions of voltage-gated sodium channel (Nav.1.3, Nav.1.8, and Nav.1.9 in NF200+ cells) as well as the pain-facilitated cellular expressions (p-P38+/peripherin+ cells, p-JNK+/peripherin+ cells, p-ERK/NF200+ cells) exhibited an identical pattern of inflammation, whereas the locomotor recovery displayed an opposite pattern of inflammation among the groups (all P < 0.0001). Combined HBO-ADMSCs therapy offered additional benefits for preserving the neurological architecture and facilitated the locomotor recovery against acute TSCI.

Funder

Chang Gung Memorial Hospital, Chang Gung University

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

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