Engraftment of bone marrow stromal cells in lipopolysaccharide-injured mouse lungs
WANG Wei, QIAN Li-Ling, LIU Hai-Pei, SUN Bo
Laboratory of Pediatric Respiratory and Critical Care Medicine, Children's Hospital andthe Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
Abstract OBJECTIVE: To explore a feasibility of engraftment of systemically transplanted bone marrow stromal cells (BMSCs) and differentiation into lung epithelial cells in lipopolysaccharides (LPS)-injured lungs. METHODS: BMSCs were isolated from bone marrow of transgenic green fluorescent protein (GFP) C57BL/6J mice and systemically administered to bone marrow-suppressed wild-type C57BL/6J mice. A mouse model of lung injury was prepared by intratracheal instillation of LPS. Recipients were assigned to four groups: intratracheal PBS + BMSCs transplantation (CM), intratracheal LPS + BMSCs transplantation (LM), intratracheal PBS + irradiation + BMSCs transplantation (CIM) and intratracheal LPS+ irradiation + BMSCs transplantation (LIM). BMSCs engraftment in recipient lungs was determined by immunofluorescent staining 14 days after BMSCs administration. Alveolar epithelial type II cells were isolated from recipient lungs and the rate of GFP positive cells was measured by flow cytometry. Expression of surfactant protein (SP)-A, SP-C and aquaporin (AQP)-5 mRNA in the lungs was evaluated by real-time PCR. RESULTS: GFP and cytokeratin positive cells were observed in lung parenchyma of the CIM and the LIM groups, but not in the CM and the LM groups. The LIM group had more positive cells than the CIM group. The rates of GFP positive cells were higher in the CIM (11.10±3.19%) and the LIM groups (14.40±2.40%) than those in the CM and the LM groups (2.82±1.03% and 3.81±0.93%, respectively; P<0.05). The LIM group had higher mRNA expression of SP-C than the CM group (2.09±0.18 vs 1.38±0.30; P<0.05). CONCLUSIONS: Donor derived BMSCs can engraft in LPS-injured lungs and differentiate into lung epithelial cells, suggesting BMSCs transplantation might contribute to lung repair.［Chin J Contemp Pediatr, 2009, 11 (5):321-327］
WANG Wei,QIAN Li-Ling,LIU Hai-Pei et al. Engraftment of bone marrow stromal cells in lipopolysaccharide-injured mouse lungs[J]. 中国当代儿科杂志, 2009, 11(05): 321-327.
WANG Wei,QIAN Li-Ling,LIU Hai-Pei et al. Engraftment of bone marrow stromal cells in lipopolysaccharide-injured mouse lungs[J]. CJCP, 2009, 11(05): 321-327.
［1］Ware LB, Matthay MA. The acute respiratory distress syndrome［J］. N Engl J Med, 2000, 342(18):1334-1349.
［2］Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. Incidence and outcomes of acute lung injury ［J］. N Engl J Med, 2005, 353(16):1685-1693.
［3］Matthay MA, Zimmerman GA, Esmon C, Bhattacharya J, Coller B, Doerschuk CM, et al. Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group ［J］. Am J Respir Crit Care Med, 2003, 167(7):1027-1035.
［4］Yu WL, Lu ZJ, Wang Y, Shi LP, Kuang FW, Qian SY, et al. Collaborative Study Group of Pediatric Respiratory Failure. The epidemiology of acute respiratory distress syndrome in pediatric intensive care units in China ［J］. Intensive Care Med, 2009, 35(1):136-143.
［5］Kitamura Y, Hashimoto S, Mizuta N, Kobayashi A, Kooguchi K, Fujiwara I, et al. Fas/FasL-dependent apoptosis of alveolar cells after lipopolysaccharide induced lung injury in mice ［J］. Am J Respir Crit Care Med, 2001, 163(3 Pt 1):762-769.
［6］Rojas M, Woods CR, Mora AL, Xu J, Brigham KL. Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses ［J］. Am J Physiol Lung Cell Mol Physiol, 2005, 288(2):L333-L341.
［7］Stripp BR, Shapiro SD. Stem cells in lung disease, repair, and the potential for therapeutic interventions: State-of-the-art and future challenges ［J］. Am J Respir Cell Mol Biol, 2006, 34(5):517-518.
［8］Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues ［J］. Science, 1997, 276(5309):71-74.
［9］Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells ［J］. Science, 1999, 284(5411):143-147.
［10］Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects ［J］. Proc Natl Acad Sci USA, 2003, 100(14):8407-8411.
［11］Yamada M, Kubo H, Kobayashi S, Ishizawa K, Numasaki M, Ueda S, et al. Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury ［J］. J Immunol, 2004, 172(2):1266-1272.
［12］Kotton DN, Ma BY, Cardoso WV, Sanderson EA, Summer RS, Williams MC, et al. Bone marrow-derived cells as progenitors of lung alveolar epithelium ［J］. Development, 2001, 128(24):5181-5188.
［13］Grove JE, Lutzko C, Priller J, Henegariu O, Theise ND, Kohn DB, et al. Marrow derived cells as vehicles for delivery of gene therapy to pulmonary epithelium ［J］. Am J Respir Cell Mol Biol, 2002, 27(6):645-651.
［14］Vernooy JH, Dentener MA, van Suylen RJ, Buurman WA, Wouters EF. Intratracheal instillation of lipopolysaccharide in mice induces apoptosis in bronchial epithelial cells ［J］. Am J Respir Cell Mol Biol, 2001, 24(5):569-576.
［15］Azizi SA, Stokes D, Augelli BJ, DiGirolamo C, Prockop DJ. Engraftment and migration of human bone marrow stromal cells implanted in the brain of albino rats-similarities to astrocyte grafts ［J］. Proc Natl Acad Sci USA, 1998, 95(7):3908-3913.
［16］Yamaguchi A, Komori T, Suda T. Regulation of osteoblast differentiation mediated by bone morphogenetic protein, hedgehogs, and Cbfa 1 ［J］. Endocrine Rev, 2001, 21(4):393-411.
［17］Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cell differentiation into neurons ［J］. J Neurosci Res, 2000, 61(4):364-370.
3.0.CO;2-C target="_blank">
［18］Jia YJ, Yang YJ, Zhou Y, Song YZ, Liu LX, Song JH, et al. Differentiation of rat bone marrow stromal cells into neuron induced by baicalin ［J］. Zhonghua Yixue Zazhi, 2002, 82(19):1337-1341.
［19］Richards RJ, Davies N, Atkins J, Orefoo VIC. Isolation, biochemical characterisation, and culture of lung type II cells of the rat ［J］. Lung, 1987, 165(3):143-158.
［20］Griffiths MJD, Bonnet D, Mjanes S. Stem cells of the alveolar epithelium［J］. Lancet, 2005, 366(9481):249-260.
［21］Zander DS, Baz MA, Cogle CR, Visner GA, Theise ND, Crawford JM. Bone marrow-derived stem-cell repopulation contributes minimally to the type II pneumocyte pool in transplanted human cells ［J］. Transplantation, 2005, 80(2):206-212.
［22］Mei SH, McCarter SD, Deng Y, Parker CH, Liles WC, Stewart DJ. Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1［J］. PLoS Med, 2007, 4(9):e269.
［23］Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung［J］.Am J Respir Cell Mol Biol, 2005, 33(2):145-152.
［24］Kotton DN, Fabian AJ, Mulligan RC. Failure of bone marrow to reconstitute lung epithelium ［J］. Am J Respir Cell Mol Biol, 2005, 33(4):328-334.
