title: Donor age negatively affects the immunoregulatory properties of both adipose and bone marrow derived mesenchymal stem cells.
abstract: OBJECTIVE
  Age negatively impacts the biologic features of mesenchymal stem cells (MSCs), including decreased expansion kinetics and differentiation potential. Clinically, donor-age may be within a wide spectrum; therefore, investigation of the role of donor's age on immunoregulatory potential is of critical importance to translate stem cell therapies from bench to bedside.
  
  
  METHODS
  Adipose and bone marrow derived MSCs (ASCs and BMSCs) were isolated in parallel from Lewis and Brown Norway rats of young (less than 4-week old) and senior groups (older than 15-month). The presentation of cells and time required for growth to 90% confluence was recorded. FACS sorting based on the expression of CD90 and CD29 double positive and CD45 CD11 double negative quantified the proportions of MSCs. After expansion, ASCs and BMSCs from different age groups were co-cultured in mixed lymphocyte reaction (MLR; Lewis vs. Brown Norway) assays. The suppression of CD3(+)CD4(+) and CD3(+)CD8(+) T cell populations by different sources of MSCs were compared.
  
  
  RESULTS
  The kinetics of cell growth was slower in old animals (17.3±2days) compared with young animals (8.8±3days), and cell morphology was irregular and enlarged in the senior groups. The yield of MSCs by FACS sorting was significantly higher in young groups compared to senior groups (p<0.02). With regard to immunoregulatory potential, senior ASCs failed to induce any CD3(+)CD4(+) T cell suppression (p>0.05). In addition, young BMSCs-induced suppression was more prominent than seniors (p<0.05).
  
  
  CONCLUSIONS
  Donor age should be taken into consideration when using recipient MSC of either bone marrow or adipose origin in clinical applications.
authors.affiliation: Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Plastic and Reconstructive Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Lehao W
authors.initials: LW
authors.lastname: Wu
authors.affiliation: Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Vascularized Composite Allotransplantation, Department of Plastic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Joani M
authors.initials: JM
authors.lastname: Christensen
authors.affiliation: Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Saami
authors.initials: S
authors.lastname: Khalifian
authors.affiliation: Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneeberger
authors.affiliation: Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Raimondi
authors.affiliation: Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Damon S
authors.initials: DS
authors.lastname: Cooney
authors.affiliation: Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: W P Andrew
authors.initials: WP
authors.lastname: Lee
authors.affiliation: Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: brandacher@jhmi.edu.
authors.forename: Gerald
authors.initials: G
authors.lastname: Brandacher
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology; D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D018845:CD11 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018920:Coculture Techniques; D019012:Integrin beta1 / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000235:genetics; D007959:Lymphocyte Culture Test, Mixed; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D018800:Thy-1 Antigens / Q000235:genetics; D014019:Tissue Donors
chemical_list: D018845:CD11 Antigens; D019012:Integrin beta1; D018800:Thy-1 Antigens; D017493:Leukocyte Common Antigens; C516771:Ptprc protein, rat
keywords: Adipose tissue; Age; Bone marrow; Immunoregulation; Mesenchymal stem cells