title: Regulation of transplanted mesenchymal stem cells by the lung progenitor niche in rats with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Stem cell transplantation is a promising method for the treatment of chronic obstructive pulmonary disease (COPD), and mesenchymal stem cells (MSCs) have clinical potential for lung repair/regeneration. However, the rates of engraftment and differentiation are generally low following MSC therapy for lung injury. In previous studies, we constructed a pulmonary surfactant-associated protein A (SPA) suicide gene system, rAAV-SPA-TK, which induced apoptosis in alveolar epithelial type II (AT II) cells and vacated the AT II cell niche. We hypothesized that this system would increase the rates of MSC engraftment and repair in COPD rats.
  
  
  METHODS
  The MSC engraftment rate and morphometric changes in lung tissue in vivo were investigated by in situ hybridization, hematoxylin and eosin staining, Masson's trichrome staining, immunohistochemistry, and real-time PCR. The expression of hypoxia inducible factor (HIF-1α) and stromal cell-derived factor-1 (SDF-1), and relationship between HIF-1α and SDF-1 in a hypoxic cell model were analyzed by real-time PCR, western blotting, and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  rAAV-SPA-TK transfection increased the recruitment of MSCs but induced pulmonary fibrosis in COPD rats. HIF-1α and SDF-1 expression were enhanced after rAAV-SPA-TK transfection. Hypoxia increased the expression of HIF-1α and SDF-1 in the hypoxic cell model, and SDF-1 expression was augmented by HIF-1α under hypoxic conditions.
  
  
  CONCLUSIONS
  Vacant AT II cell niches increase the homing and recruitment of MSCs to the lung in COPD rats. MSCs play an important role in lung repair and promote collagen fiber deposition after induction of secondary damage in AT II cells by rAAV-SPA-TK, which involves HIF-1α and SDF-1 signaling.
authors.forename: Wan-Guang
authors.initials: WG
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Shi
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Wu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Mei
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Xu
authors.forename: Zhen-Xiang
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095, Jie Fang Road, Han Kou District, Wuhan, Hubei 430030, China. huilanz_76@163.com.
authors.forename: Hui-Lan
authors.initials: HL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D054377:Chemokine CXCL12 / Q000096:biosynthesis*; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit