Gene expression profiling of human mesenchymal stem cells chemotactically induced with CXCL12

Abstract

In situ tissue engineering is a promising approach in regenerative medicine, with the possibility that adult stem or progenitor cells will be guided chemotactically to a tissue defect and subsequently differentiate into the surrounding tissue type. Mesenchymal stem cells (MSC) represent attractive candidate cells. Chemokines such as CXCL12 (SDF-1alpha) chemoattract MSC, but little is known about the molecular processes involved in the chemotaxis and migration of MSC. In this study, MSC recruitment by CXCL12 was investigated by genome-wide microarray analysis. The dose-dependent migration potential of bone-marrow-derived MSC toward CXCL12 was measured in an in vitro assay, with a maximum being recorded at a concentration of 1,000 nM CXCL12. Microarray analysis of MSC stimulated with CXCL12 and non-stimulated controls showed 30 differentially expressed genes (24 induced and six repressed). Pathway analysis revealed 11 differentially expressed genes involved in cellular movement and cytokine-cytokine receptor interaction, including those for migratory inducers such as the chemokines CXCL8 and CCL26, the leukocyte inhibitory factor, secretogranin II, and prostaglandin endoperoxide synthase 2. These results were confirmed by real-time polymerase chain reaction for selected genes. The obtained data provide further insights into the molecular mechanisms involved in chemotactic processes in cell migration and designate CXCL12 as a promising candidate for in situ recruitment in regenerative therapies.

Nuclear ReceptorsNur77andNurr1Modulate Mesenchymal Stromal Cell Migration

“…[25,26]). Expression of Nur77 has not been described in MSC before, whereas increased expression of Nurr1 was observed in adult BMSC exposed to SDF-1a [44] or CXCL7 [45]. In these 2 studies, no functional experiments on Nurr1 were performed.…”

Stromal cell derived factor-1α enhances bone formation based on in situ recruitment: a histologic and histometric study in rabbit calvaria

“…Enhanced recruitment of autologous stem cells may improve tissue responsiveness and jumpstart stem cell participation in healing (Thevenot et al 2010). Taken together with what is already known about MSC recruitment and differentiation, these results suggest that guiding MSCs to sites of damaged tissue is a promising approach for in situ regenerative medicine (Stich et al 2009). Our observations support the notion that SDF-1a is a promising candidate for in situ recruitment in regenerative therapies.…”

Osteoporosis and ageing affects the migration of stem cells and this is ameliorated by transfection with CXCR4

“…The cells will subsequently differentiate into the surrounding tissue type and affect repair at the injury site. 18 Poor homing ability of the stem cells to bone could result in a significant reduction in bone formation which ultimately contributes to osteoporosis. 19 …”