Migratory response of mesenchymal stem cells to macrophage migration inhibitory factor and its antagonist as a function of colony-forming efficiency.
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abstract
Human mesenchymal stem cells (MSCs) are capable of repairing pulmonary disorders, but their efficacy is limited by poor engraftment. A strategy is proposed to augment MSC migration to lung tissue by antagonizing macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine. Recombinant MIF (85 ng/ml) inhibited in vitro chemokinesis of multipotent MSCs by nearly 50 and 20% for donor preparations with colony-forming efficiencies of 22 +/- 4% and 66 +/- 3%, respectively (P < 0.05). The small-molecule MIF antagonist, (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1, 85 microg/ml), restored MSC migration for all donors to levels found in the absence of MIF. At this concentration, ISO-1 increased migration to conditioned medium from bronchial epithelial cell cultures by >or=3-fold for all donor MSC preparations (P < 0.05). Transcript levels for the MIF receptor, CD74, in MSCs were independent of colony-forming efficiency. These data suggest that MIF and its antagonists may be relevant to the control of MSC homing and efficacy of stem cell therapies in a variety of clinical scenarios.
published proceedings
Biotechnol Lett
altmetric score
3
author list (cited authors)
Fischer-Valuck, B. W., Barrilleaux, B. L., Phinney, D. G., Russell, K. C., Prockop, D. J., & O'Connor, K. C.
citation count
25
complete list of authors
Fischer-Valuck, Benjamin W||Barrilleaux, Bonnie L||Phinney, Donald G||Russell, Katie C||Prockop, Darwin J||O'Connor, Kim C