Functional Expression of N-formyl Peptide Receptors in Human Bone Marrow-derived Mesenchymal Stem Cells

¹ Departments of Medicine and Genetics, Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana

^* To whom correspondence should be addressed. E-mail: gwang{at}lsuhsc.edu.

	Abstract

Tissue injury enhances homing and engraftment of mesenchymal stem cells (MSCs). However, the mechanisms of how MSCs sense the signals released by injured tissues and migrate towards injury sites have not been fully defined. In the current report, we investigated if human MSCs express the N-formyl peptide receptor (FPR) and the formyl peptide receptor-like-1 (FPRL1). These receptors bind to N-formylated peptides whereby phagocytes migrate to inflammatory sites and fibroblasts repopulate wounds to remodel the damaged tissues. Reverse-transcription PCR demonstrated that MSCs express both FPR and FPRL1 at the transcriptional level. Flow cytometric analyses revealed expression of both receptors at the protein level. Fusion of the enhanced green fluorescence protein (eGFP) to the C-terminus of each receptor showed localization to the cell surface. Moreover, MSCs responded to stimulation by N-formyl methionyl leucyl phenylalanine (fMLP), a prototypic N-formyl peptide, demonstrating rapid intracellular calcium mobilization that can be blocked by pertussis toxin or cyclosporine H. Interestingly, the fMLP-stimulated MSCs had an enhanced adhesion to extracellular matrix protein-coated surfaces. In addition, MSCs migrated toward gradients of increasing fMLP concentration, indicating that the receptors are functionally involved in positive chemotaxis to formylated peptides. Therefore, the N-formyl peptide receptors present in MSCs may play an important role in signaling stem cell adhesion, migration and homing to injured tissue for repair. Such a mechanism can be potentially exploited to direct the stem cells to target specific tissue sites for therapy.