title: Mesenchymal stem cells of different origin: Comparative evaluation of proliferative capacity, telomere length and pluripotency marker expression.
abstract: OBJECTIVE
  In vitro expansion changes replication and differentiation capacity of mesenchymal stem cells (MSCs), increasing challenges and risks, while limiting the sufficient number of MSCs required for cytotherapy. Here, we characterized and compared proliferation, differentiation, telomere length and pluripotency marker expression in MSCs of various origins.
  
  
  METHODS
  Immunophenotyping, proliferation and differentiation assays were performed. Pluripotency marker (Nanog, Oct-4, SOX-2, SSEA-4) expression was determined by immunofluorescence. Quantitative PCR was performed for relative telomere length (RTL) analyses, while expression of relevant genes for pluripotency markers, differentiation state (Cbfa1, human placental alkaline phosphatase, peroxisome proliferator activated receptor, Sox9 and Collagen II a1), and telomerase reverse transcriptase (hTERT) was determined by semiquantitative RT-PCR.
  
  
  RESULTS
  Peripheral blood MSCs (PB-MSCs) and umbilical cord MSCs (UC-MSCs) showed the highest, while periodontal ligament MSCs (PDL-MSCs) and adipose tissue MSCs (AT-MSCs) the lowest values of both the replication potential and RTL. Although MSCs from exfoliated deciduous teeth (SHEDs), PDL-MSCs and AT-MSCs showed higher mRNA expression of pluripotency markers, all MSCs expressed pluripotency marker proteins. SHEDs and PDL-MSCs showed prominent capacity for osteogenesis, PB-MSCs and UC-MSCs showed strengthened adipogenic differentiation potential, while AT-MSCs displayed similar differentiation into both lines.
  
  
  CONCLUSIONS
  The MSCs populations derived from different sources, although displaying similar phenotype, exhibited high degree of variability regarding biological properties related to their self-renewal and differentiation capacity. These data indicate that for more accurate use in cell therapy, individualities of MSCs isolated from different tissues should be identified and taken into consideration when planning their use in clinical protocols.
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Drenka
authors.initials: D
authors.lastname: Trivanović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jauković
authors.affiliation: Institute of Human Genetics, School of Dentistry, University of Belgrade, Belgrade, Serbia.
authors.forename: Branka
authors.initials: B
authors.lastname: Popović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Krstić
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Slavko
authors.initials: S
authors.lastname: Mojsilović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Okić-Djordjević
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Kukolj
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Hristina
authors.initials: H
authors.lastname: Obradović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Santibanez
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia. Electronic address: dianab@imi.bg.ac.rs.
authors.forename: Diana
authors.initials: D
authors.lastname: Bugarski
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000166:cytology; D015415:Biomarkers / Q000032:analysis; D001773:Blood Cells / Q000502:physiology; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D008022:Ligaments / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D010012:Osteogenesis / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D016615:Telomere / Q000648:ultrastructure*; D059506:Telomere Shortening; D014094:Tooth, Deciduous / Q000166:cytology; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D015415:Biomarkers
keywords: Differentiation; Mesenchymal stem cells; Pluripotency; Relative telomere length