on October 13, 2005
Published online before print October 13, 2005, doi: 10.1161/01.ATV.0000190701.92007.6d
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Submitted on March 27, 2005
Accepted on September 7, 2005
Novel Autologous Cell Therapy in Ischemic Limb Disease Through Growth Factor Secretion by Cultured Adipose Tissue-Derived Stromal Cells
Hironori Nakagami *;
From the Division of Gene Therapy Science (H.N., S.I., T.N., Y.T., Y.K., Y.S., K.T., Y.K.), Graduate School of Medicine, Osaka University; the Medical Center for Translational Research (H.N., K.M.), Osaka University Hospital; the Division of Clinical Gene Therapy (R.M.), Graduate School of Medicine, Osaka University; and the Department of Geriatric Medicine (Y.T., T.O.), Graduate School of Medicine, Osaka University, Osaka, Japan
* To whom correspondence should be addressed. E-mail: nakagami{at}gts.med.osaka-u.ac.jp.
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 with anti-CD31 antibody. However, injected ADSC did not correspond to CD31, von Willebrand factor, and 
-smooth muscle actin-positive cells in ischemic tissue.
Conclusion--These adipose tissue-derived cells demonstrated potential as angiogenic cell therapy for ischemic disease, which appears to be mainly achieved by their ability to secrete angiogenic growth factors.
Key words: adipose tissue • angiogenesis • growth factors • HGF • VEGF
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