Novel Autologous Cell Therapy in Ischemic Limb Disease Through Growth Factor Secretion by Cultured Adipose Tissue–Derived Stromal Cells

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Abstract
Objective— The delivery of autologous progenitor cells into ischemic tissue of patients is emerging as a novel therapeutic option. Here, we report the potential impact of cultured adipose tissue–derived cells (ADSC) on angiogenic cell therapy. Method and Results— ADSC were isolated from C57Bl/6 mouse inguinal adipose tissue and showed high expression of ScaI and CD44, but not c-kit, Lin, CD34, CD45, CD11b, and CD31, compatible with that of mesenchymal stem cells from bone marrow. In coculture conditions with ADSC and human aortic endothelial cells (ECs) under treatment with growth factors, ADSC significantly increased EC viability, migration and tube formation mainly through secretion of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). At 4 weeks after transplantation of ADSC into the ischemic mouse hindlimb, the angiogenic scores were improved in the ADSC-treated group, which were evaluated with blood flow by laser Doppler imaging (LDI) and capillary density by immunostaining... The adipose tissue–derived cells (ADSCs) induced angiogenesis through secretion of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in coculture with endothelial cells or ischemic mouse hindlimb model. These results demonstrated the potential of ADSC as angiogenic cell therapy for ischemic disease.