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.
Highlights
According to statistics, 70% of the population will be plagued by lower back pain in life caused by disc degeneration disease (DDD), which leads to a serious public health problem [1,2,3]
Disc degeneration is characterized by a reduction of nucleus pulposus cells (NPCs) and their extracellular matrix (ECM), and NPCs are replaced by cells of a more fibroblast-like phenotype in the degenerated intervertebral discs (IVDs) [6]
We found that all of the NP cells and the extracellular matrix in the nucleus pulposus region were stained by immunohistochemistry collagen II and aggrecan, and the transplanted Bone mesenchymal stem cells (BMSCs) surround the positive extracellular matrix
Summary
70% of the population will be plagued by lower back pain in life caused by disc degeneration disease (DDD), which leads to a serious public health problem [1,2,3]. Curative treatment for DDD is a major challenge because of limited regeneration of the IVD itself. Bone mesenchymal stem cells (BMSCs) hold great promise in IVD regeneration [8,9,10,11]. Due to the lack of blood vessels and the special hypertonic and hypoxic environment of IVDs [19, 20], the survival rate and repair ability of transplanted stem cells cultured under common culture conditions are poor [21, 22]. As the hypertonic and hypoxic environment can reduce activity and vitality of transplanted stem cells [23, 24], a way to bolster the transplanted stem cell survival and treatment effects is needed urgently
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