Abstract
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.
Highlights
Background/introduction Severe chronic peripheral arterial disease (PAD) manifests as critical limb ischemia (CLI) with a 5-year mortality rate >70%
We show that pulsed focused ultrasound noninvasively establishes a “molecular zip-code” of locally upregulated chemoattractants that lead to enhanced homing permeability and retention of IV-infused Mesenchymal stem cells (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 improve limb perfusion
Summary
Background/introduction Severe chronic peripheral arterial disease (PAD) manifests as critical limb ischemia (CLI) with a 5-year mortality rate >70%. Reestablishment of perfusion in critical limb ischemia model with pulsed focused ultrasound (pFUS) and mesenchymal stem cells in aged mice 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.
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