Comparison of the therapeutic effects of human and mouse adipose-derived stem cells in a murine model of lipopolysaccharide-induced acute lung injury.
BACKGROUND
Adipose-derived stem cells (ASCs) have emerged as important regulators of inflammatory/immune responses in vitro and in vivo and represent attractive candidates for cell-based therapies for diseases that involve excessive inflammation. Acute lung injury (ALI) is an inflammatory condition for which treatment is mainly supportive due to lack of effective therapies. In this study, the therapeutic effects of ASC-based therapy were assessed in vivo by comparison of the anti-inflammatory properties of both human and murine ASCs in a mouse model of lipopolysaccharide (LPS)-induced ALI.


METHODS
Human ASCs (hASCs) or mouse ASCs (mASCs) were delivered to C57Bl/6 mice (7.5 × 105 total cells/mouse) by oropharyngeal aspiration (OA) four hours after the animals were challenged with lipopolysaccharide (15 mg/kg). Mice were sacrificed 24 and 72 hours after LPS exposure, and lung histology examined for evaluation of inflammation and injury. Bronchoalveolar lavage fluid (BALF) was analyzed to determine total and differential cell counts, total protein and albumin concentrations, and myeloperoxidase (MPO) activity. Cytokine expression in the injured lungs was measured at the steady-state mRNA levels and protein levels for assessment of the degree of lung inflammation.


RESULTS
Both human and mouse ASC treatments provided protective anti-inflammatory responses. There were decreased levels of leukocyte (for example neutrophil) migration into the alveoli, total protein and albumin concentrations in BALF, and MPO activity after the induction of ALI following both therapies. Additionally, cell therapy with both cell types effectively suppressed the expression of proinflammatory cytokines and increased the anti-inflammatory cytokine interleukin 10 (IL-10). Overall, the syngeneic mASC therapy had a more potent therapeutic effect than the xenogeneic hASC therapy in this model.


CONCLUSIONS
Treatment with hASCs or mASCs significantly attenuated LPS-induced acute lung injury in mice. These results suggest a potential benefit for using an ASC-based therapy to treat clinical ALI and may possibly prevent the development of acute respiratory distress syndrome (ARDS).
Shijia
S
Zhang
Svitlana D
SD
Danchuk
Kathleen Mp
KM
Imhof
Julie A
JA
Semon
Brittni A
BA
Scruggs
Ryan W
RW
Bonvillain
Amy L
AL
Strong
Jeffrey M
JM
Gimble
Aline M
AM
Betancourt
Deborah E
DE
Sullivan
Bruce A
BA
Bunnell
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000503:physiopathology; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
D008070:Lipopolysaccharides; D016753:Interleukin-10; D009195:Peroxidase