title: EphA2 is a biomarker of hMSCs derived from human placenta and umbilical cord.
abstract: OBJECTIVE
  The heterogeneous nature of mesenchymal stem cells (MSCs) and the absence of known MSC-specific biomarkers make it challenging to define MSC phenotypes and characteristics. In this study, we compared the phenotypic and functional features of human placenta-derived MSCs with those of human dermal fibroblasts in vitro in order to identify a biomarker that can be used to increase the purity of MSCs in a primary culture of placenta-derived cells.
  
  
  METHODS
  Liquid chromatography-tandem mass spectrometry analysis was used to analyze and compare the proteome of human placenta-derived MSCs with that of fibroblasts. Quantitative real-time polymerase chain reaction, immunofluorescence, and flow cytometry were used to determine expression levels of EphA2 in placenta-derived MSCs. EphA2-positive cells were enriched by magnetic-activated cell sorting or with a cell sorter. An shRNA-mediated EphA2 knockdown was used to assess the role of EphA2 in MSC response to Tumor necrosis factor (TNF)-α stimulation.
  
  
  RESULTS
  Analysis of proteomics data from MSCs and fibroblasts resulted in the identification of the EphA2 surface protein biomarker, which could reliably distinguish MSCs from fibroblasts. EphA2 was significantly upregulated in placenta-derived MSCs when compared to fibroblasts. EphA2 played an important role in MSC migration in response to inflammatory stimuli, such as TNF-α. EphA2-enriched MSCs were also more responsive to inflammatory stimuli in vitro when compared to unsorted MSCs, indicating a role for EphA2 in the immunomodulatory functionality of MSCs.
  
  
  CONCLUSIONS
  EphA2 can be used to distinguish and isolate MSCs from a primary culture of placenta-derived cells. EphA2-sorted MSCs exhibited superior responsiveness to TNF-α signaling in an inflammatory environment compared with unsorted MSCs or MSC-like cells.
authors.affiliation: Stem Cell Research Department, Meridigen Biotech Co. Ltd., Taipei, Taiwan.
authors.forename: Shih-Pei
authors.initials: SP
authors.lastname: Shen
authors.affiliation: Stem Cell Research Department, Meridigen Biotech Co. Ltd., Taipei, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Liu
authors.affiliation: Stem Cell Research Department, Meridigen Biotech Co. Ltd., Taipei, Taiwan.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Stem Cell Research Department, Meridigen Biotech Co. Ltd., Taipei, Taiwan.
authors.forename: Yuan-Tsung
authors.initials: YT
authors.lastname: Li
authors.affiliation: Stem Cell Research Department, Meridigen Biotech Co. Ltd., Taipei, Taiwan.
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Fung-Wei
authors.initials: FW
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Le-Ming
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Cardinal Tien Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan. Electronic address: senwen1955@yahoo.com.tw.
authors.forename: Sen-Wen
authors.initials: SW
authors.lastname: Teng
authors.affiliation: Stem Cell Research Department, Meridigen Biotech Co. Ltd., Taipei, Taiwan. Electronic address: yogi@meridigen.com.
authors.forename: Yogi
authors.initials: Y
authors.lastname: Hsuan
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D036104:Receptor, EphA2 / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014470:Umbilical Cord / Q000166:cytology*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D036104:Receptor, EphA2
keywords: EphA2; biomarker; fibroblast; immunomodulation; mesenchymal stem cells