Transplantation of Hypoxic-Preconditioned Bone Mesenchymal Stem Cells Retards Intervertebral Disc Degeneration via Enhancing Implanted Cell Survival and Migration in Rats

Weiheng Wang; Yang Wang; Guoying Deng; Jun Ma; Xiaodong Huang; Jiangming Yu; Yanhai Xi; Xiaojian Ye

doi:10.1155/2018/7564159

Transplantation of Hypoxic-Preconditioned Bone Mesenchymal Stem Cells Retards Intervertebral Disc Degeneration via Enhancing Implanted Cell Survival and Migration in Rats

Stem Cells Int. 2018 Feb 14:2018:7564159. doi: 10.1155/2018/7564159. eCollection 2018.

Authors

Weiheng Wang¹, Yang Wang², Guoying Deng³, Jun Ma¹, Xiaodong Huang¹, Jiangming Yu¹, Yanhai Xi¹, Xiaojian Ye¹

Affiliations

¹ Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
² Department of Orthopaedics, Nanjing General Hospital, Nanjing 210000, China.
³ Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.

Abstract

Objective: Special hypoxic and hypertonic microenvironment in intervertebral discs (IVDs) decreases the treatment effect of cell transplantation. We investigated the hypothesis that hypoxic preconditioning (HP) could improve the therapeutic effect of bone mesenchymal stem cells (BMSCs) to IVD degeneration.

Methods: BMSCs from green fluorescent protein-transgenic rats were pretreated with cobalt chloride (CoCl₂, 100 μM, 24 h) for hypoxic conditions in vitro. Apoptosis (related pathways of caspase-3 and bcl-2) and migration (related pathways of HIF-1α and CXCR4) were detected in BMSCs. In vivo, BMSCs and HP BMSCs (H-BMSCs) were injected into the rat model of IVD degeneration. The IVD height, survival, migration, and differentiation of transplanted BMSCs and matrix protein expression (collagen II, aggrecan, and MMP-13) were tested.

Results: H-BMSCs could extensively decrease IVD degeneration by increasing IVD height and collagen II and aggrecan expressions when compared with BMSCs. Significantly, more GFP-positive BMSCs were observed in the nucleus pulposus and annulus fibrosus regions of IVD. HP could significantly decrease BMSC apoptosis (activating bcl-2 and inhibiting caspase-3) and improve BMSC migration (increasing HIF-1α and CXCR4) in vitro.

Conclusion: HP could significantly enhance the capacity of BMSCs to repair DDD by increasing the survival and migration of implanted cells and increasing matrix protein expression.