title: Transcriptional profiling of interleukin-2-primed human adipose derived mesenchymal stem cells revealed dramatic changes in stem cells response imposed by replicative senescence.
abstract: Inflammation is a double-edged sword with both detrimental and beneficial consequences. Understanding of the mechanisms of crosstalk between the inflammatory milieu and human adult mesenchymal stem cells is an important basis for clinical efforts. Here, we investigate changes in the transcriptional response of human adipose-derived stem cells to physiologically relevant levels of IL-2 (IL-2 priming) upon replicative senescence. Our data suggest that replicative senescence might dramatically impede human mesenchymal stem cell (MSC) function via global transcriptional deregulation in response to IL-2. We uncovered a novel senescence-associated transcriptional signature in human adipose-derived MSCs hADSCs after exposure to pro-inflammatory environment: significant enhancement of the expression of the genes encoding potent growth factors and cytokines with anti-inflammatory and migration-promoting properties, as well as genes encoding angiogenic and anti-apoptotic promoting factors, all of which could participate in the establishment of a unique microenvironment. We observed transcriptional up-regulation of critical components of the nitric oxide synthase pathway (iNOS) in hADSCs upon replicative senescence suggesting, that senescent stem cells can acquire metastasis-promoting properties via stem cell-mediated immunosuppression. Our study highlights the importance of age as a factor when designing cell-based or pharmacological therapies for older patients and predicts measurable biomarkers characteristic of an environment that is conducive to cancer cells invasiveness and metastasis.
authors.affiliation: Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Niu
authors.affiliation: S.D. Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.
authors.forename: Aibek
authors.initials: A
authors.lastname: Smagul
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: S.D. Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.
authors.forename: Aiman
authors.initials: A
authors.lastname: Sadvakas
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sha
authors.affiliation: Cardiac Development and Repair Department, National Center for Cardiovascular Research (CNIC), Madrid, Spain.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Pérez
authors.affiliation: S.D. Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.
authors.forename: Aliya
authors.initials: A
authors.lastname: Nussupbekova
authors.affiliation: S.D. Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.
authors.forename: Aday
authors.initials: A
authors.lastname: Amirbekov
authors.affiliation: S.D. Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.
authors.forename: Akan A
authors.initials: AA
authors.lastname: Akanov
authors.affiliation: Cardiac Development and Repair Department, National Center for Cardiovascular Research (CNIC), Madrid, Spain.
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Gálvez
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.|PanAmerican Bioinformatics Institute, Santa Marta, Magdalena, Colombia.
authors.forename: I King
authors.initials: IK
authors.lastname: Jordan
authors.affiliation: Aelan Cell Technologies, Inc, San Francisco, CA, USA.
authors.forename: Victoria V
authors.initials: VV
authors.lastname: Lunyak
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D060066:Protein Interaction Maps / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins
keywords: Gerotarget; IL-2; aging; cancer; immunomodulation; mesenchymal stem cells