Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking

Kelly S. Schweitzer, Brian H. Johnstone, Jana Garrison, Natalia I. Rush, Scott Cooper, Dmitry Traktuev, Dongni Feng, Jeremy J. Adamowicz, Mary Van Demark, Amanda J. Fisher, Krzysztof Kamocki, Mary Beth Brown, Robert Presson, Hal Broxmeyer, Keith L. March, Irina Petrache

Research output: Contribution to journalArticle

107 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)215-225
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume183
Issue number2
DOIs
StatePublished - Jan 15 2011

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Lung Injury
Stem Cells
Smoking
Smoke
Tobacco Products
Lung
Emphysema
Endothelial Cells
Therapeutic Uses
Therapeutics
Blood Vessels
Apoptosis
Vascular Endothelial Growth Factor Receptor
Adult Stem Cells
Conditioned Culture Medium
Hematopoietic Stem Cells
Weight Loss
Intercellular Signaling Peptides and Proteins
Cell Death
Bone Marrow

Keywords

  • Cell death
  • Chronic obstructive
  • Endothelium
  • Human
  • Pulmonary disease
  • Regenerative medicine

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking. / Schweitzer, Kelly S.; Johnstone, Brian H.; Garrison, Jana; Rush, Natalia I.; Cooper, Scott; Traktuev, Dmitry; Feng, Dongni; Adamowicz, Jeremy J.; Van Demark, Mary; Fisher, Amanda J.; Kamocki, Krzysztof; Brown, Mary Beth; Presson, Robert; Broxmeyer, Hal; March, Keith L.; Petrache, Irina.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 183, No. 2, 15.01.2011, p. 215-225.

Research output: Contribution to journalArticle

Schweitzer, KS, Johnstone, BH, Garrison, J, Rush, NI, Cooper, S, Traktuev, D, Feng, D, Adamowicz, JJ, Van Demark, M, Fisher, AJ, Kamocki, K, Brown, MB, Presson, R, Broxmeyer, H, March, KL & Petrache, I 2011, 'Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking', American Journal of Respiratory and Critical Care Medicine, vol. 183, no. 2, pp. 215-225. https://doi.org/10.1164/rccm.201001-0126OC
Schweitzer, Kelly S. ; Johnstone, Brian H. ; Garrison, Jana ; Rush, Natalia I. ; Cooper, Scott ; Traktuev, Dmitry ; Feng, Dongni ; Adamowicz, Jeremy J. ; Van Demark, Mary ; Fisher, Amanda J. ; Kamocki, Krzysztof ; Brown, Mary Beth ; Presson, Robert ; Broxmeyer, Hal ; March, Keith L. ; Petrache, Irina. / Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking. In: American Journal of Respiratory and Critical Care Medicine. 2011 ; Vol. 183, No. 2. pp. 215-225.
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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.",
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