Transplantation of CXCR4 Overexpressed Mesenchymal Stem Cells Augments Regeneration in Degenerated Intervertebral Discs

SDF-1/CXCR4 chemotaxis signals play important roles in regulating the stem cell-based tissue regeneration. The aim of this research is to evaluate whether high expression of CXCR4 enhances the migration of mesenchymal stem cells (MSCs) and increases the efficiency of intervertebral disc (IVD) regeneration. MSCs overexpressing CXCR (CXCR4-MSC) were created by lentiviral-CXCR4-vect transfection, labeled with SPIO, and transplanted into rabbit degenerative IVD induced by annulus puncture. X-ray and T2-weighted MR images of the spine were obtained at 0, 8, and 16 weeks post-transplantation. The transplanted stem cells were traced by both MR imaging and Prussian blue staining. The stem cell-based IVD degeneration was evaluated by quantifying the expression of aggrecan and type II collagen. The in vitro chemotaxis test was performed to study the migration of CXCR4-MSCs to the supplement of SDF-1. The CXCR4-overexpressing MSCs stably elevated the expression of CXCR4 and increased the migration to SDF-1. The SPIO-labeled CXCR4-MSC could be detected within the IVD by MRI till 16 weeks post-transplantation. Prussian blue staining evidenced more SPIO-positive cells within the IVD transplanted with CXCR4-MSCs. Compared to the control group, loss of disc height was slowed while the mRNA expression of aggrecan and type II collagen was increased by MSC transplantation, especially in the IVD supplemented with CXCR4-MSCs. CXCR4 overexpression promoted MSC retention within the IVD and enhanced the stem cell-based IVD regeneration. The SDF-1/CXCR4 chemotaxis signals might help provide a new perspective to understand stem cell migration and infiltration within the degenerated IVD.