Abstract
The recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to damaged tissues and sites of inflammation is an essential step for clinical therapy. However, the signals regulating the motility of these cells are still not fully understood. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is known to have a variety of biological effects on various cells. Here, we investigated the roles of S1P and S1P receptors (S1PRs) in migration of human BMSCs. We found that S1P exerted a powerful migratory action on human BMSCs. Moreover, by employing RNA interference technology and pharmacological tools, we demonstrated that S1PR1 and S1PR3 are responsible for S1P-induced migration of human BMSCs. In contrast, S1PR2 mediates the inhibition of migration. Additionally, we explored the downstream signaling pathway of the S1P/S1PRs axis and found that activation of S1PR1 or S1PR3 increased migration of human BMSCs through a Gi/extracellular regulated protein kinases 1/2- (ERK1/2-) dependent pathway, whereas activation of S1PR2 decreased migration through the Rho/Rho-associated protein kinase (ROCK) pathway. In conclusion, we reveal that the S1P/S1PRs signaling axis regulates the migration of human BMSCs via a dual-directional mechanism. Thus, selective modulation of S1PR's activity on human BMSCs may provide an effective approach to immunotherapy or tissue regeneration.
Highlights
Mesenchymal stem cells (MSCs) have been shown to affect both innate and adaptive immune response [1,2,3]
Since S1PR1–3 are the S1P cell surface receptor subtypes that are involved in S1P-mediated biological activities; we investigated whether these receptors are expressed in human bone marrowderived mesenchymal stem cells (BMSCs)
We used siRNA technology to knock down S1PR1 and S1PR3 expression in human BMSCs
Summary
Mesenchymal stem cells (MSCs) have been shown to affect both innate and adaptive immune response [1,2,3]. They have been identified and isolated from multiple tissues, including adipose tissue, umbilical cord, bone marrow, muscle, and fetal liver [4]. In all of these preclinical and clinical studies, the engraftment of BMSCs into damaged tissues via migration to suppress immune responses or enhance tissue repair/regeneration is a crucial process for clinical therapy [13]. For BMSCs to migrate to and target a specific tissue, they require the right combination of signaling molecules from the injured tissue and the corresponding receptors on BMSCs [13, 14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
