Modifying strategies for SDF-1/CXCR4 interaction during mesenchymal stem cell transplantation

Abstract

Mesenchymal stem cell (MSC) transplantation is regarded as a promising candidate for the treatment of ischaemic heart disease. The major hurdles for successful clinical translation of MSC therapy are poor survival, retention, and engraftment in the infarcted heart. Stromal cell-derived factor-1/chemokine receptor 4 (SDF-1/CXCR4) constitutes one of the most efficient chemokine/chemokine receptor pairs regarding cell homing. In this review, we mainly focused on previous studies on how to regulate the SDF-1/CXCR4 interaction through various priming strategies to maximize the efficacy of mesenchymal stem cell transplantation on ischaemic hearts or to facilitate the required effects. The strengthened measures for enhancing the therapeutic efficacy of the SDF-1/CXCR4 interaction for mesenchymal stem cell transplantation included the combination of chemokines and cytokines, hormones and drugs, biomaterials, gene engineering, and hypoxia. The priming strategies on recipients for stem cell transplantation included ischaemic conditioning and device techniques.

Knockdown SENP1 Suppressed the Angiogenic Potential of Mesenchymal Stem Cells by Impacting CXCR4-Regulated MRTF-A SUMOylation and CCN1 Expression

“…Together with the results that CXCR4 overexpression upregulated CCN1 level, and SENP1 knockdown suppressed its expression, these data indicate that CXCR4 was likely to play a role upstream of MRTF-A. CXCR4 is a chemokine receptor specific for stromal cell-derived factor-1 (SDF-1), which regulates numerous activities such as chemotaxis, adhesion, and cell proliferation [ 47 , 48 ]. SDF-1α/CXCR4 signaling was reported previously that played a crucial role in the process of pathological neovascularization [ 49 ].…”

Therapeutic gene delivery by mesenchymal stem cell for brain ischemia damage: Focus on molecular mechanisms in ischemic stroke

“…The chemokine SDF-1, which is essential for MSC homing, and its receptor CXCR4 are essential for MSC migration during ischemia. [231][232][233] The SDF-1/CXCR axis can be activated for stem cell homing in two ways: by upregulating the quantity of SDF-1 in the brain and by upregulating the expression of CXCR4 on MSCs. One possibility is exogenous SDF-1 or an increase in SDF-1 mRNA or protein expression.…”

Cellular modifications and biomaterial design to improve mesenchymal stem cell transplantation

“…Transduced MSCs with elevated CXCR4 levels show increased migration towards the SDF-1 chemokine gradient, and improved homing to the infarcted myocardium compared to non-transduced MSCs. 117,118 Similarly, CXCR4-overexpressing bone marrow-derived rat MSCs exhibit enhanced chemotactic and paracrine characteristics. Injecting these MSCs into an LPS-induced acute lung injury model improves homing in target tissues and suppresses inflammatory molecules.…”