Surface tethering of stromal cell-derived factor-1α carriers to stem cells enhances cell homing to ischemic muscle

Mesenchymal stem cells are promising medicine for treating diseases and tissue defects because of their innate ability to secrete therapeutic factors. Intravenous delivery of stem cells, although favored for its minimal invasiveness, is often plagued by low cellular engraftment in the target tissue. To this end, this study hypothesizes that in situ activation of cellular expression of CXC chemokine 4 (CXCR4) would significantly improve cellular migration to injured tissue. This hypothesis was examined by tethering the surface of stem cells with poly(D,L-lactide-co-glycolide)-block-hyaluronic acid (HA) particles containing stromal cell-derived factor-1α, a model chemokine to sensitize CXCR4. The HA blocks in the particles enhanced the association rate constant to stem cells by 3.3-fold, and in turn, increased the number of cells expressing CXCR4 receptors. Consequently, these cells displayed 1.2-fold higher transendothelial migration in vitro and 1.7-fold greater trafficking to the ischemic hindlimb of a mouse than that of the untethered cells. The surface of mesenchymal stem cells was tethered with poly(D,L-lactide-co-glycolide)-block-hyaluronic acid particles releasing stromal cell-derived factor-1α, a model chemokine to sensitize CXC chemokine 4 (CXCR4). Consequently, the expression of CXCR4 in the stem cells and the number of cells positive for CXCR4 were increased. These MSCs demonstrated an enhanced transendothelial migration in vitro and an improved migration to the ischemic muscle following intravenous administration in vivo. [Display omitted]