Paracrine factors of multipotent stromal cells ameliorate lung injury in an elastase-induced emphysema model.
Multipotent stromal cells (MSCs) ameliorate several types of lung injury. The differentiation of MSCs into specific cells at the injury site has been considered as the important process in the MSC effect. However, although MSCs reduce destruction in an elastase-induced lung emphysema model, MSC differentiation is relatively rare, suggesting that MSC differentiation into specific cells does not adequately explain the recuperation observed. Humoral factors secreted by MSCs may also play an important role in ameliorating emphysema. To confirm this hypothesis, emphysema was induced in the lungs of C57BL/6 mice by intratracheal elastase injection 14 days before intratracheal MSC or phosphate-buffered saline (PBS) administration. Thereafter, lungs were collected at several time points and evaluated. Our results showed that MSCs reduced the destruction in elastase-induced emphysema. Furthermore, double immunofluorescence staining revealed infrequent MSC engraftment and differentiation into epithelial cells. Real-time PCR showed increased levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF). Real-time PCR and western blotting showed enhanced production of secretory leukocyte protease inhibitor (SLPI) in the lung. In-vitro coculture studies confirmed the in vivo observations. Our findings suggest that paracrine factors derived from MSCs is the main mechanism for the protection of lung tissues from elastase injury.
Katsha
Ahmed M
AM
Department of Respiratory Medicine, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Japan.
Ohkouchi
Shinya
S
Xin
Hong
H
Kanehira
Masahiko
M
Sun
Ruowen
R
Nukiwa
Toshihiro
T
Saijo
Yasuo
Y
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D004646:Emphysema / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D004815:Epidermal Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects; D005455:Fluorescent Antibody Technique / Q000379:methods; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D039902:Multipotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D010196:Pancreatic Elastase; D011650:Pulmonary Alveoli / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000378:metabolism; D015854:Up-Regulation
D053583:Interleukin-1beta; D053481:Secretory Leukocyte Peptidase Inhibitor; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D010196:Pancreatic Elastase