Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking.
BACKGROUND
Adipose-derived stem cells express multiple growth factors that inhibit endothelial cell apoptosis, and demonstrate substantial pulmonary trapping after intravascular delivery.


OBJECTIVE
We hypothesized that adipose stem cells would ameliorate chronic lung injury associated with endothelial cell apoptosis, such as that occurring in emphysema.


METHODS
Therapeutic effects of systemically delivered human or mouse adult adipose stem cells were evaluated in murine models of emphysema induced by chronic exposure to cigarette smoke or by inhibition of vascular endothelial growth factor receptors.


RESULTS
Adipose stem cells were detectable in the parenchyma and large airways of lungs up to 21 days after injection. Adipose stem cell treatment was associated with reduced inflammatory infiltration in response to cigarette smoke exposure, and markedly decreased lung cell death and airspace enlargement in both models of emphysema. Remarkably, therapeutic results of adipose stem cells extended beyond lung protection by rescuing the suppressive effects of cigarette smoke on bone marrow hematopoietic progenitor cell function, and by restoring weight loss sustained by mice during cigarette smoke exposure. Pulmonary vascular protective effects of adipose stem cells were recapitulated by application of cell-free conditioned medium, which improved lung endothelial cell repair and recovery in a wound injury repair model and antagonized effects of cigarette smoke in vitro.


CONCLUSIONS
These results suggest a useful therapeutic effect of adipose stem cells on both lung and systemic injury induced by cigarette smoke, and implicate a lung vascular protective function of adipose stem cell derived paracrine factors.
Schweitzer
Kelly S
KS
Division of Pulmonary and Critical Care Medicine, Indiana University, Indianapolis, IN 46202-5120, USA.
Johnstone
Brian H
BH
Garrison
Jana
J
Rush
Natalia I
NI
Cooper
Scott
S
Traktuev
Dmitry O
DO
Feng
Dongni
D
Adamowicz
Jeremy J
JJ
Van Demark
Mary
M
Fisher
Amanda J
AJ
Kamocki
Krzysztof
K
Brown
Mary Beth
MB
Presson
Robert G
RG
Broxmeyer
Hal E
HE
March
Keith L
KL
Petrache
Irina
I
D000273:Adipose Tissue / Q000166:cytology* / Q000637:transplantation; D053687:Adult Stem Cells / Q000637:transplantation*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control; D055370:Lung Injury / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D012907:Smoking / Q000009:adverse effects*; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods; D015431:Weight Loss