title: Periostin enhances adipose-derived stem cell adhesion, migration, and therapeutic efficiency in Apo E deficient mice with hind limb ischemia.
abstract: BACKGROUND
  Therapeutic angiogenesis by transplantation of autologous/allogeneic adipose-derived stem cells (ADSCs) is a potential approach for severe ischemic diseases. However, poor viability, adhesion, migration and differentiation limit the therapeutic efficiency after the cells were transplanted into the targeted area. Periostin, an extracellular matrix protein, exhibits a critical role in wound repair as well as promotes cell adhesion, survival, and angiogenesis.
  
  
  METHODS
  ADSCs were obtained and genetically engineered with periostin gene (P-ADSCs). The viability, proliferation, migration, and apoptosis of P-ADSCs under hypoxia were analyzed. Moreover, P-ADSCs were implanted into Apo E deficient mice with hind limb ischemia. The Laser Doppler perfusion index, immunofluorescence, and histological pathology assay were tested to evaluate the therapeutic effects. The associated molecular mechanism of periostin on the proliferation, adhesion, migration, and differentiation of ADSCs was also analyzed.
  
  
  RESULTS
  The in vitro studies have shown that periostin-transfected ADSCs (P-ADSCs) promoted viability, proliferation, and migration of ADSCs. Apoptosis of ADSCs was inhibited under hypoxic conditions. The Laser Doppler perfusion index was significantly higher in the P-ADSCs group compared with that in the ADSC and control groups after 4 weeks. Immunofluorescence and histological pathology assay showed that the P-ADSCs were in and around the ischemic sites, and some cells differentiated into capillaries and endothelium. Microvessel densities were significantly improved in P-ADSCs group compared with those in the control group. The molecular mechanisms that provide the beneficial effects of periostin were connected with the upregulated expression of integrinβ1/FAK/PI3K/Akt/eNOS signal pathway and the increased secretion of growth factors.
  
  
  CONCLUSIONS
  Overexpression of periostin by gene transfection on ADSCs promotes survival, migration, and therapeutic efficiency, which will bring new insights into the treatment of critical limb ischemia.
authors.affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, People's Republic of China. jinbaoqin@163.com.
authors.forename: Jinbao
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, People's Republic of China. jsbuck520@163.com.
authors.forename: Fukang
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, People's Republic of China. zhiyoupeng@163.com.
authors.forename: Zhiyou
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, People's Republic of China. ykaichuang@163.com.
authors.forename: Kaichuang
authors.initials: K
authors.lastname: Ye
authors.affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, People's Republic of China. cinder_13@126.com.
authors.forename: Xinrui
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, People's Republic of China. 708973502@qq.com.
authors.forename: Lijia
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, People's Republic of China. ryshuiyb@126.com.
authors.forename: Mier
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, People's Republic of China. xinwu_lu@163.com.|Vascular Center of Shanghai JiaoTong University, Shanghai, 200011, People's Republic of China. xinwu_lu@163.com.
authors.forename: Xinwu
authors.initials: X
authors.lastname: Lu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D007511:Ischemia / Q000378:metabolism* / Q000628:therapy*; D023821:Limb Salvage; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; C082838:Postn protein, mouse