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Adipose Stem Cell Treatment in Mice Attenuates Lung and Systemic Injury Induced by Cigarette Smoking
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Adipose Stem Cell Treatment in Mice Attenuates Lung and Systemic Injury Induced by Cigarette Smoking
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Journal Article
Adipose Stem Cell Treatment in Mice Attenuates Lung and Systemic Injury Induced by Cigarette Smoking
2011
Overview
Abstract
Rationale
Adipose-derived stem cells express multiple growth factors that inhibit endothelial cell apoptosis, and demonstrate substantial pulmonary trapping after intravascular delivery.
Objectives
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.
Measurements and Main 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.
Publisher
Oxford University Press,American Thoracic Society
Subject
/ Adipose Tissue - transplantation
/ Adult Stem Cells - transplantation
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Animals
/ B. Chronic Obstructive Pulmonary Disease
/ Biological and medical sciences
/ Body fat
/ Chronic obstructive pulmonary disease
/ Female
/ Humans
/ Inflammation - physiopathology
/ Inflammation - prevention & control
/ Lung Injury - physiopathology
/ Lungs
/ Mice
/ Pulmonary Alveoli - physiopathology
/ Pulmonary Emphysema - etiology
/ Pulmonary Emphysema - physiopathology
/ Pulmonary Emphysema - therapy
/ Stem Cell Transplantation - methods
/ Transfusions. Complications. Transfusion reactions. Cell and gene therapy
/ Transplantation, Heterologous - methods
/ Transplantation, Homologous - methods
