title: Leukocyte-Reduced Platelet-Rich Plasma Alters Protein Expression of Adipose Tissue-Derived Mesenchymal Stem Cells.
abstract: BACKGROUND
  Application of platelet-rich plasma and stem cells has become important in regenerative medicine. Recent literature supports the use of platelet-rich plasma as a cell culture media supplement to stimulate proliferation of adipose tissue-derived mesenchymal stem cells. The underlying mechanism of proliferation stimulation by platelet-rich plasma has not been investigated so far.
  
  
  METHODS
  Adipose tissue-derived mesenchymal stem cells were cultured in α-minimal essential medium supplemented with platelet-rich plasma or fetal calf serum. Cell proliferation was assessed with cell cycle kinetics using flow cytometric analyses after 48 hours. Differences in proteome expression of the adipose tissue-derived mesenchymal stem cells were analyzed using a reverse-phase protein array to quantify 214 proteins. Complementary Ingenuity Pathways Analysis and gene set enrichment analysis were performed using protein data, and confirmed by Western blot analysis.
  
  
  RESULTS
  A higher percentage of adipose tissue-derived mesenchymal stem cells in the S phase in the presence of platelet-rich plasma advocates the proliferation stimulation. Ingenuity Pathways Analysis and gene set enrichment analysis confirm the involvement of the selected proteins in the process of cell growth and proliferation. Ingenuity Pathways Analysis revealed a participation in the top-ranked canonical pathways PI3K/AKT, PTEN, ILK, and IGF-1. Gene set enrichment analysis identified the authors' protein set as being part of significantly regulated protein sets with the focus on cell cycle, metabolism, and the Kyoto Encyclopedia of Genes and Genomes transforming growth factor-β signaling pathway.
  
  
  CONCLUSIONS
  The present study provides evidence that platelet-rich plasma stimulates proliferation and induces a unique change in the proteomic profile of adipose tissue-derived mesenchymal stem cells. The interpretation of altered expression of regulatory proteins represents a step forward toward achieving good manufacturing practice-compliant criteria for cell-based strategies.
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Markus
authors.initials: M
authors.lastname: Loibl
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Siegmund
authors.initials: S
authors.lastname: Lang
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hanke
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Marietta
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Michaela
authors.initials: M
authors.lastname: Huber
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Gero
authors.initials: G
authors.lastname: Brockhoff
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Silvan
authors.initials: S
authors.lastname: Klein
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Michael
authors.initials: M
authors.lastname: Nerlich
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Peter
authors.initials: P
authors.lastname: Angele
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Lukas
authors.initials: L
authors.lastname: Prantl
authors.affiliation: Regensburg, Germany; and Davos and Basel, Switzerland.|From the Departments of Trauma Surgery and Obstetrics and Gynecology and the Center of Plastic, Hand, and Reconstructive Surgery, University Medical Center Regensburg; the AO Research Institute Davos, AO Foundation; and the Department of Orthopedic Surgery, University Hospital Basel.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gehmert
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D053657:Platelet-Rich Plasma / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D011506:Proteins