caa a22 4500 445292393 CHVBK 20180317142532.0 cr unu---uuuuu 170323e20100601xx s 000 0 eng 10.1007/s11626-010-9279-1 doi (NATIONALLICENCE)springer-10.1007/s11626-010-9279-1 Activation of CD74 inhibits migration of human mesenchymal stem cells [Elektronische Daten] [Bonnie Barrilleaux, Benjamin Fischer-Valuck, Jennifer Gilliam, Donald Phinney, Kim O'Connor] Therapeutic administration of mesenchymal stem cells (MSCs) by systemic delivery utilizes the innate ability of the cells to home to damaged tissues, but it can be an inefficient process due to a limited knowledge of cellular cues that regulate migration and homing. Our lab recently discovered that a potent pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), inhibits MSC migration. Because MIF may act on multiple cellular targets, an activating antibody (CD74Ab) was employed in this study to examine the effect of one MIF receptor, CD74 (major histocompatibility complex class II-associated invariant chain), on MSC motility. CD74 activation inhibits in a dose-dependent manner up to 90% of in vitro migration of MSCs at 40μg/ml CD74Ab (p < 0.001), with consistent effects observed among three MSC donor preparations. A blocking peptide from the C-terminus of CD74 eliminates the effect of CD74Ab on MSCs. This suggests that MIF may act on MSCs, at least in part, through CD74. Late-passage MSCs exhibit less chemokinesis than those at passage 2. However, MSCs remain responsive to CD74 activation during ex vivo expansion: MSC migration is inhibited ∼2-fold in the presence of 5µg/ml CD74Ab at passage 9 vs. ∼3-fold at passage 2 (p < 0.001). Consistent with this result, there were no significant differences in CD74 expression at all tested passages or after CD74Ab exposure. Targeting CD74 to regulate migration and homing potentially may be a useful strategy to improve the efficacy of a variety of MSC therapies, including those that require ex vivo expansion. The Society for In Vitro Biology, 2010 Mesenchymal stem cells nationallicence CD74 nationallicence Major histocompatibility complex class II-associated invariant chain nationallicence Chemokinesis nationallicence Migration nationallicence Barrilleaux Bonnie Department of Chemical and Biomolecular Engineering, Tulane University, Lindy Boggs Center Room 300, 70118, New Orleans, LA, USA aut Fischer-Valuck Benjamin Department of Chemical and Biomolecular Engineering, Tulane University, Lindy Boggs Center Room 300, 70118, New Orleans, LA, USA aut Gilliam Jennifer Department of Chemical and Biomolecular Engineering, Tulane University, Lindy Boggs Center Room 300, 70118, New Orleans, LA, USA aut Phinney Donald Department of Molecular Therapeutics, The Scripps Research Institute, 33458, Jupiter, FL, USA aut O'Connor Kim Department of Chemical and Biomolecular Engineering, Tulane University, Lindy Boggs Center Room 300, 70118, New Orleans, LA, USA aut In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/6(2010-06-01), 566-572 1071-2690 46:6<566 2010 46 11626 https://doi.org/10.1007/s11626-010-9279-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11626-010-9279-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Barrilleaux Bonnie Department of Chemical and Biomolecular Engineering, Tulane University, Lindy Boggs Center Room 300, 70118, New Orleans, LA, USA aut NATIONALLICENCE 700 1- Fischer-Valuck Benjamin Department of Chemical and Biomolecular Engineering, Tulane University, Lindy Boggs Center Room 300, 70118, New Orleans, LA, USA aut NATIONALLICENCE 700 1- Gilliam Jennifer Department of Chemical and Biomolecular Engineering, Tulane University, Lindy Boggs Center Room 300, 70118, New Orleans, LA, USA aut NATIONALLICENCE 700 1- Phinney Donald Department of Molecular Therapeutics, The Scripps Research Institute, 33458, Jupiter, FL, USA aut NATIONALLICENCE 700 1- O'Connor Kim Department of Chemical and Biomolecular Engineering, Tulane University, Lindy Boggs Center Room 300, 70118, New Orleans, LA, USA aut NATIONALLICENCE 773 0- In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/6(2010-06-01), 566-572 1071-2690 46:6<566 2010 46 11626 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer