Hyaluronic Acid Mediated Mesenchymal Stem Cell Migration

Much is known about CD34+ stem cell migration to areas of hypoxia due to secretion of SDF-1 (CXCL12) by the hypoxia tissue. Migration towards the CXCL12 gradient has been documented in diverse situations ranging from post-myocardial infarction CD34 mobilization to homing of hematopoietic stem cells to the bone marrow niche during transplantation. However signals that cause migration of mesenchymal stem cells to areas of injury are not as well known.

In a recent paper (Herrera et al. Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury. Kidney Int. 2007 May 16) the importance of hyaluronic acid production by injured tissue as a mediator of mesenchymal stem cell homing was demonstrated. Hyaluronic acid is a large glycosaminoglycan which serves as one of the important components of the extracellular matrix. Additionally, hyaluronic acid is known to possess numerous functions including immune activation, promotion of proliferation, migration, and intracellular signaling.

The researchers used the glycerol-induced mouse model of acute renal failure to show that intravenous administration of mesenchymal stem cells led to acceleration of renal healing and that this acceleration would be blocked if anti-CD44 antibodies were added. The researchers did several other in vitro and in vivo experiments to show that the CD44-hyaluronic acid interaction is critical for the migration of mesenchymal stem cells to area of kidney injury.

This study is interesting in light of other findings (Avigdor et al. CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood. 2004 Apr 15;103(8):2981-9) that demonstrate the importance of hyaluronic acid in chemoattraction of CD34 stem cells into the body marrow in cooperation with CXCL12.