Human Umbilical Cord Blood‐Derived Mesenchymal Stromal Cells Display a Novel Interaction between P‐Selectin and Galectin‐1

Abstract

Human multipotent mesenchymal stromal/stem cells (MSCs) have been shown to exert immunomodulatory properties that have great potential in therapies for various inflammatory and autoimmune disorders. However, intravenous delivery of these cells is followed by massive cell entrapment in the lungs and insufficient homing to target tissues or organs. In targeting to tissues, MSCs and other therapeutic cells employ similar mechanisms as leucocytes, including a cascade of rolling and adhesion steps mediated by selectins, integrins and their ligands. However, the mechanisms of MSCs homing are not well understood. We discovered that P-selectin (CD62P) binds to umbilical cord blood (UCB)-derived MSCs independently of the previously known sialyl Lewis x (sLex)-containing ligands such as P-selectin glycoprotein ligand-1 (PSGL-1, CD162). By biochemical assays, we identified galectin-1 as a novel ligand for P-selectin. Galectin-1 has previously been shown to be a key mediator of the immunosuppressive effects of human MSCs. We conclude that this novel interaction is likely to play a major role in the immunomodulatory targeting of human UCB-derived MSCs.

Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement

“…However, as MSCs do not express PSGL-1, they must use a different ligand to interact with P-selectin. One study has identified galectin-1 as one such candidate (Suila et al., 2014). Another study has identified CD24 as a potential P-selectin ligand in adipose tissue-derived stromal cells, which resemble MSCs (Bailey et al., 2009).…”

Concise Review: MSC Adhesion Cascade—Insights into Homing and Transendothelial Migration

“…). Indeed, MSCs have been shown to express glycoproteins and galectin‐1 , which may represent alternative P‐selectin ligands. Furthermore, interaction of MSCs with P‐selectin might be mediated by a bridging mechanism involving platelets.…”

Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress

“…However, as most understanding of migration and homing mechanisms derived from studies evaluating leucocytes migrating into inflamed tissues, the fact that MSCs do not express the hematopoietic cell E-/L-selectin ligand (HCELL) [135], a specialized glycoform of CD44 on the migrating cell, as well as the P-selectin glycoprotein ligand-1 (PSGL-1) [135], raises the question of which selectin exactly employed by MSCs. One study has identified galectin-1 [138] as one such candidate, and another study has identified CD24 as a potential P-selectin ligand [139]. Following the initiation of tethering step, activation step is facilitated typically by G protein-coupled chemokine receptors in response to inflammatory signals.…”