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

Abstract

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.

SDF-1/CXCR4 Augments the Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells in the Treatment of Lipopolysaccharide-Induced Liver Injury by Promoting Their Migration Through PI3K/Akt Signaling Pathway

“…Upon arrival at the injury site, BMSCs play an active role in attenuating liver injury, including significantly decreasing the size of the liver injury area, inhibiting liver cell apoptosis, and simultaneously promoting liver cell proliferation. These findings are accordance with previous reports of the positive effects of BMSCs in other pathological conditions 21 – 34 . Thus, from this study, we extended the scope of pathological conditions that could benefit from BMSCs transplanting therapy to LPS or sepsis-induced acute liver injury.…”

Effects of Stromal Cell-Derived Factor-1α Secreted in Degenerative Intervertebral Disc on Activation and Recruitment of Nucleus Pulposus-Derived Stem Cells

“…For example, SDF-1 α has been shown to promote the survival of oligodendrocyte and trophoblast precursors [50, 51]. Wei et al [21] found that overexpression of CXCR4 could promote MSC retention in the degenerative IVD that enhanced the stem cell-based regeneration. In the present study, we also demonstrated that SDF-1 α could improve the late proliferation of NPSCs.…”

“…It was documented that the increased SDF-1 α in the osteoarthritis tissue could promote the recruitment of CXCR4-positive MSCs into the injured cartilage [18]. The expression of SDF-1 α was also reported to be upregulated in the human degenerative IVD [19, 20], and overexpression of its receptor CXCR4 could promote MSC retention in the degenerative IVD and enhance stem cell-based IVD regeneration [21]. In addition, the hyaluronan-based delivery of SDF-1 α significantly boosted the recruitment of MSCs into the degenerative IVD in an ex vivo organ culture [22].…”

A Global Pictorial Assessment of the Intervertebral Disc Cell in Several Species Reveals a Remarkable Biodiversity in this Cell Type which should be taken into Account in Experimental Studies on Intervertebral Disc Repair

“…These have potent chemotactic activity and their expression is upregulated in the degenerate IVD [59], moreover intradiscal administration of SDF-1/CXCR4 over-expressing stem cells promotes repair of degenerate IVDs [60]. SDF-1/CXCR4 mediated cell signalling promotes digit regeneration in mice a process driven by BMP-2 [61,62].…”