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Severe chronic peripheral arterial disease (PAD) manifests as critical limb ischemia (CLI) with a 5-year mortality rate >70%. Mesenchymal stem cells (MSC) show promise to minimize CLI progression and restore perfusion in experimental models, but approaches suffer from minimal homing to ischemic tissue and require clinically impractical direct injections of cells. We show that pulsed focused ultrasound (pFUS) noninvasively establishes a “molecular zip-code” of locally upregulated chemoattractants (i.e. cytokines, chemokines, cell adhesion molecules) that lead to enhanced homing permeability and retention of IV-infused MSC to pFUS-treated muscle. This study investigated if pFUS could enhance MSC homing in a CLI model in aged mice and whether they could ultimately improve limb perfusion.

Reestablishment of perfusion in critical limb ischemia model with pulsed focused ultrasound (pFUS) and mesenchymal stem cells in aged mice