Transplanted hUCB-MSCs migrated to the damaged area by SDF-1/CXCR4 signaling to promote functional recovery after traumatic brain injury in rats

Abstract

Transplanted human umbilical cord mesenchymal stem cells (hUC-MSCs) have exhibited considerable therapeutic potential for traumatic brain injury (TBI). However, how hUC-MSCs migrating to the injury region and the mechanism of hUC-MSCs promoting functional recovery after TBI are still unclear. In this study, we investigated whether stromal cell-derived factor-1 (SDF-1) was involved in the hUC-MSCs migration and the possible mechanisms that might be involved in the beneficial effect on functional recovery. In vitro experiments demonstrated that SDF-1 induces a concentration-dependent migration of hUC-MSCs. Furthermore, pre-treatment with the CXCR4-specific antagonist AMD3100 significantly prevented the migration of hUC-MSCs in vitro. We found that the expression of SDF-1 increased significantly around the damaged area. Transplanted hUC-MSCs were localized to regions where SDF-1 was highly expressed. Additionally, our results showed that hUC-MSCs-treated animals showed significantly improved functional recovery compared with controls. In hUC-MSCs-transplanted group, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells were decreased and BrdU-positive cells were significantly increased compared with control group, more of BrdU-positive cells co-localized with GFAP. These suggest that SDF-1 plays an important role in the migration of hUC-MSCs to the damaged area and hUC-MSCs are beneficial for functional recovery after TBI.

Advances in CXCR7 Modulators

“…The mechanism of action for agonists or antagonists may be more related to CXCL12-mediated effects than CXCR7. CXCL12 levels are increased in most pathological conditions that CXCR7 is overexpressed in, including tumors [112,113], rheumatoid arthritis [34,114,115], stroke [116,117], multiple sclerosis [118], traumatic brain injury [119][120][121] and obesity [48]. An exception is that decreased blood levels of CXCL12 are observed in Alzheimer's disease [122].…”

Danhong Injection Enhances the Therapeutic Efficacy of Mesenchymal Stem Cells in Myocardial Infarction by Promoting Angiogenesis

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Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy

“…For instance, the C-X-C motif chemokine ligand 12 (CXCL12) is a frequent triggering factor at the site of injury. It has been demonstrated that a subpopulation of MSCs expresses the C-X-C chemokine receptor type 4 (CXCR4) that binds to its ligand, the CXCL12, to mediate cell migration (Wynn et al, 2004;Ma et al, 2015). Aside from CXCR4, MSCs express other chemokine receptors, such as CCR1, CCR2, CCR4, CCR7, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, and CX3CR1 (Sordi et al, 2005;Von Luttichau et al, 2005;Honczarenko et al, 2006;Ringe et al, 2007).…”