bone marrow stem cells expressing keratinocyte growth factor via an inducible lentivirus protects against bleomycin-induced pulmonary fibrosis骨髓干细胞通过诱导表达角质细胞生长因子的慢病毒预防bleomycin-induced肺纤维化.pdfVIP

Bone Marrow Stem Cells Expressing Keratinocyte Growth Factor via an Inducible Lentivirus Protects against Bleomycin-Induced Pulmonary Fibrosis 1,2 1 1 3,4 3,4 1 Susana Aguilar , Chris J. Scotton , Katrina McNulty , Emma Nye , Gordon Stamp , Geoff Laurent , Dominique Bonnet2.*, Sam M. Janes1.* 1 Centre for Respiratory Research, Rayne Institute, University College London, London, United Kingdom, 2 Hematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom, 3 Experimental Pathology Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom, 4 Department of Histopathology, Imperial College London, London, United Kingdom Abstract Many common diseases of the gas exchange surface of the lung have no specific treatment but cause serious morbidity and mortality. Idiopathic Pulmonary Fibrosis (IPF) is characterized by alveolar epithelial cell injury, interstitial inflammation, fibroblast proliferation and collagen accumulation within the lung parenchyma. Keratinocyte Growth Factor (KGF, also known as FGF-7) is a critical mediator of pulmonary epithelial repair through stimulation of epithelial cell proliferation. During repair, the lung not only uses resident cells after injury but also recruits circulating bone marrow-derived cells (BMDC). Several groups have used Mesenchymal Stromal Cells (MSCs) as therapeutic vectors, but little is known about the potential of Hematopoietic Stem cells (HSCs). Using an inducible lentiviral vector (Tet-On) expressing KGF, we were able to efficiently transduce both MSCs and HSCs, and demonstrated that KGF expression is induced in a regula