However, previous clinical applications of SDF-1-based therapies have faced significant challenges, particularly in terms of stability and delivery in vivo. A phase 2B clinical trial involving 109 PAD patients with critical limb ischemia found no significant improvement in outcomes with intramuscular plasmid encoding SDF-1 in conjunction with endovascular surgery [15]. This evidence concerns the gene CXCL12 and peripheral arterial disease.