Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4

Abstract

BackgroundMesenchymal stem cells (MSCs) represent an important source for cell therapy in regenerative medicine. MSCs have shown promising results for repair of damaged tissues in various degenerative diseases in animal models and also in human clinical trials. However, little is known about the factors that could enhance the migration and tissue-specific engraftment of exogenously infused MSCs for successful regenerative cell therapy. Previously, we have reported that interleukin-3 (IL-3) prevents bone and cartilage damage in animal models of rheumatoid arthritis and osteoarthritis. Also, IL-3 promotes the differentiation of human MSCs into functional osteoblasts and increases their in-vivo bone regenerative potential in immunocompromised mice. However, the role of IL-3 in migration of MSCs is not yet known. In the present study, we investigated the role of IL-3 in migration of human MSCs under both in-vitro and in-vivo conditions.MethodsMSCs isolated from human bone marrow, adipose and gingival tissues were used for in-vitro cell migration, motility and wound healing assays in the presence or absence of IL-3. The effect of IL-3 preconditioning on expression of chemokine receptors and integrins was examined by flow cytometry and real-time PCR. The in-vivo migration of IL-3-preconditioned MSCs was investigated using a subcutaneous matrigel-releasing stromal cell-derived factor-1 alpha (SDF-1α) model in immunocompromised mice.ResultsWe observed that human MSCs isolated from all three sources express IL-3 receptor-α (IL-3Rα) both at gene and protein levels. IL-3 significantly enhances in-vitro migration, motility and wound healing abilities of MSCs. Moreover, IL-3 preconditioning upregulates expression of chemokine (C-X-C motif) receptor 4 (CXCR4) on MSCs, which leads to increased migration of cells towards SDF-1α. Furthermore, CXCR4 antagonist AMD3100 decreases the migration of IL-3-treated MSCs towards SDF-1α. Importantly, IL-3 also induces in-vivo migration of MSCs towards subcutaneously implanted matrigel-releasing-SDF-1α in immunocompromised mice.ConclusionsThe present study demonstrates for the first time that IL-3 has an important role in enhancing the migration of human MSCs through regulation of the CXCR4/SDF-1α axis. These findings suggest a potential role of IL-3 in improving the efficacy of MSCs in regenerative cell therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0618-y) contains supplementary material, which is available to authorized users.

Improved therapeutics of modified mesenchymal stem cells: an update

“…On the background of their previous report that, IL-3 prevents bone and cartilage damage, and increases the differentiation potential of MSCs into functional osteoblasts, Barhanpurkar-Naik et al [83] further investigate the role of IL-3 in the migration of MSCs. They report that MSCs conditioned with IL-3, overexpress CXCR4 which causes increased migration towards SDF-1α (i.e.…”

Osteoarthritic Milieu Affects Adipose‐Derived Mesenchymal Stromal Cells

“…Different molecules are involved in or necessary for the different steps in the homing process, and chemokines receptors (G‐protein coupled receptors) represent the main group . It has been extensively demonstrated that the CXCR4–stromal‐derived factor‐1 (CXCL12/SDF‐1) axis is critical for bone marrow homing, and a number of the other cytokines and growth factors such as CCL2/MCP1, TNFα, CXCL10/IP10 have been shown to increase migration in vitro …”

Accelerated infected wound healing by topical application of encapsulated Rosemary essential oil into nanostructured lipid carriers

“…It is well known that exposure of mesenchymal stem cells with IL-3 could increase cell migration and wound closure. On the other hand, Barhanpurkar-Naik showed that IL-3 stimulates cell migration in the mesenchymal stem and also fastens wound closure [33]. In this context, the level of the IL-3 was higher in the REO-NLCs-treated animals.…”

“…REO-NLCs increased SDF-1a in comparison to the control group. It is accepted that SDF-1a is significantly increased in the injured tissues and facilitates the migration and engraftment of circulation of CXCR4-positive cells [33]. With regards to increasing the level of IL-3 and SDF-1a in REO-NLCs-treated animals, it can be claimed that therapeutic gels helped to trigger the wound healing.…”