title: Transplantation of IL-10-transfected endothelial progenitor cells improves retinal vascular repair via suppressing inflammation in diabetic rats.
abstract: OBJECTIVE
  We aimed to evaluate the effect of IL-10 gene transfection on endothelial progenitor cells (EPCs) under inflammatory conditions, and explore the therapeutic potential of IL-10-transfected EPC transplantation on nonproliferative diabetic retinopathy (NPDR).
  
  
  METHODS
  Lentivirus vectors encoding IL-10 were constructed and introduced into EPCs isolated from rat bone marrow. After exposure to recombinant rat TNF-α, abilities of nontransfected EPCs (non-EPCs) and EPCs transfected with normal control lentivirus (EPCs-GFP) or IL-10 expressing lentivirus (EPCs-IL-10-GFP) were assessed, including migration, adhesion, and tube formation. IL-10 production by EPCs-IL-10-GFP was determined by ELISA. Following 12 weeks after establishment of diabetes, diabetic rats were randomly injected with non-EPCs, EPCs-GFP, or EPCs-IL-10-GFP via tail vein. Expression of inflammatory factors and factors associated with nuclear factor-kappa B (NF-kB) signal pathway, retinal histological analysis, and retinal vascular permeability were assessed 2 weeks after transplantation.
  
  
  RESULTS
  The detrimental effects of TNF-ɑ on the abilities of EPCs were significantly attenuated in EPCs-IL-10-GFP compared with non-EPCs and EPCs-GFP. The concentration of IL-10 in the EPCs-IL-10-GFP group was significantly higher than the non-EPCs and EPCs-GFP groups. Additionally, transplantation of EPCs-IL-10-GFP significantly inhibited inflammatory factors expression and activation of NF-kB signal pathway, improved retinal histological changes, and attenuated retinal vascular permeability.
  
  
  CONCLUSIONS
  In conclusion, transplantation of IL-10-transfected EPCs significantly improved EPCs-mediated retinal vascular repair and subsequently suppressed NPDR progression. This was associated with inflammation suppression, at least partly via inhibiting the NF-kB signal pathway. Transplantation of IL-10-transfected EPCs may be a new strategy for treatment of NPDR.
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin, 300052, China.|Shenyang Aier Eye Hospital, NO.11, Shiyi Wei Road, Shenyang, 110003, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin, 300052, China.|Department of Ophthalmology, The First Hospital Affiliated of Anhui Medical University, Hefei, Anhui, 230022, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin, 300052, China.
authors.forename: Xiangda
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin, 300052, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin, 300052, China.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin, 300052, China.
authors.forename: Zhuhong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin, 300052, China. phuayan2000@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier / Q000502:physiology; D015153:Blotting, Western; D002199:Capillary Permeability / Q000502:physiology; D017690:Cell Transplantation; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D066026:Endothelial Progenitor Cells / Q000378:metabolism / Q000637:transplantation*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology; D016753:Interleukin-10 / Q000235:genetics*; D016086:Lentivirus / Q000235:genetics; D008297:Male; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D031300:Retinal Vasculitis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D012171:Retinal Vessels / Q000502:physiology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Endothelial progenitor cells; IL-10; Inflammation; Nonproliferative diabetic retinopathy; Vascular repair