Autologous transplantation of adipose tissue-derived stromal cells ameliorates pulmonary emphysema.
Adipose tissue is a useful tool for management of most complex cardiothoracic problems, including the reinforcement of damaged lungs, and adipose tissue-derived stromal cells (ASCs) have been suggested to secrete hepatocyte growth factor (HGF), a multipotent regenerative factor that contributes to the repair process after lung injury. The goal of this study was to demonstrate the therapeutic impact of autologous transplantation of ASCs through HGF supplementation for the enhancement of alveolar repair in a rat model of emphysema. ASCs were isolated from inguinal subcutaneous fat pads and characterized by flow cytometry. Cultured ASC were found to secrete significantly larger amounts of HGF (15 112 +/- 1628 pg per 10(6) cells) than other angiogenic factors. Transplantation of ASCs into elastase-treated emphysema models induced a significant increase in endogenous HGF expression in lung tissues with a small amount of increase in other organs, with the high levels lasting for up to 4 weeks after transplantation. Further, alveolar and vascular regeneration were significantly enhanced via inhibition of alveolar cell apoptosis, enhancement of epithelial cell proliferation and promotion of angiogenesis in pulmonary vasculature, leading to restoration of pulmonary function affected by emphysema. These data suggest that autologous ASC cell therapy may have a therapeutic potential for pulmonary emphysema, through inducing HGF expression selectively in injured lung tissues.
Shigemura
N
N
Division of Cardiothoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Okumura
M
M
Mizuno
S
S
Imanishi
Y
Y
Nakamura
T
T
Sawa
Y
Y
D000273:Adipose Tissue; D000818:Animals; D004195:Disease Models, Animal; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011650:Pulmonary Alveoli / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D014182:Transplantation, Autologous
D018809:Proliferating Cell Nuclear Antigen; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor