Adipose Stem Cell Treatment in Mice Attenuates Lung and Systemic Injury Induced by Cigarette Smoking
- 15 January 2011
- journal article
- Published by American Thoracic Society in American Journal of Respiratory and Critical Care Medicine
- Vol. 183 (2), 215-225
- https://doi.org/10.1164/rccm.201001-0126oc
Abstract
Adipose-derived stem cells express multiple growth factors that inhibit endothelial cell apoptosis, and demonstrate substantial pulmonary trapping after intravascular delivery. We hypothesized that adipose stem cells would ameliorate chronic lung injury associated with endothelial cell apoptosis, such as that occurring in emphysema. 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. 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. 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.Keywords
This publication has 45 references indexed in Scilit:
- Matrix modulation of compensatory lung regrowth and progenitor cell proliferation in miceAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2010
- Bone Marrow Progenitor Cells Induce Endothelial Adherens Junction Integrity by Sphingosine-1-Phosphate–Mediated Rac1 and Cdc42 SignalingCirculation Research, 2009
- IFATS Collection: Human Adipose Tissue-Derived Stem Cells Induce Angiogenesis and Nerve Sprouting Following Myocardial Infarction, in Conjunction with Potent Preservation of Cardiac FunctionThe International Journal of Cell Cloning, 2009
- Targeted Induction of Lung Endothelial Cell Apoptosis Causes Emphysema-like Changes in the MouseJournal of Biological Chemistry, 2008
- Intranasal HGF Administration Ameliorates the Physiologic and Morphologic Changes in Lung EmphysemaMolecular Therapy, 2008
- IFATS Collection: Adipose Stromal Cell Differentiation Is Reduced by Endothelial Cell Contact and Paracrine Communication: Role of Canonical Wnt SignalingThe International Journal of Cell Cloning, 2008
- Suppression of Hepatocyte Growth Factor Production Impairs the Ability of Adipose-Derived Stem Cells to Promote Ischemic Tissue RevascularizationThe International Journal of Cell Cloning, 2007
- IFN- -dependent DNA Injury and/or Apoptosis Are Critical in Cigarette Smoke-induced Murine EmphysemaProceedings of the American Thoracic Society, 2006
- Yield of human adipose-derived adult stem cells from liposuction aspiratesCytotherapy, 2004
- Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based TherapiesTissue Engineering, 2001