Defective phenotype of mesenchymal stem cells in patients with systemic lupus erythematosus

被引:92
作者
Nie, Y. [1 ]
Lau, C. S. [1 ]
Lie, A. K. W. [1 ]
Chan, G. C. F. [2 ]
Mok, M. Y. [1 ]
机构
[1] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China
[2] Univ Hong Kong, Queen Mary Hosp, Dept Paediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China
关键词
autoimmune disease; mesenchymal stem cells; systemic lupus erythematosus; telomerase; MARROW STROMAL CELLS; TELOMERASE ACTIVITY; IN-VITRO; AUTOIMMUNE-DISEASES; PROGENITOR CELLS; T-LYMPHOCYTE; TRANSPLANTATION; PROLIFERATION; MICROENVIRONMENT; EXPANSION;
D O I
10.1177/0961203309361482
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Systemic lupus erythematosus (SLE) has been considered as stem cell disorder. The objective of this study was to examine the phenotype, growth and immunomodulatory effect of mesenchymal stem cells (MSCs) from SLE patients compared with those from age-and sex-matched healthy donors. MSCs were expanded from bone marrow aspirate and were examined for morphological appearance, quantified in different passages to determine growth rate and evaluated for ability of adipogenesis and osteogenesis. Telomerase activity was measured by telomerase repeat amplification protocol. The immunomodulatory effect of MSCs was evaluated by mixed lymphocyte reaction. MSCs from SLE patients were found to be bigger and flattened in appearance after passage 3 and demonstrated slower growth rate compared with fibroblast-like MSCs from normal controls. These cells were not able to reach confluence after passage 4. Telomerase activity was upregulated in five SLE patients mostly with active disease compared with two with negative expression with lesser activity. MSCs from SLE patients were, otherwise, comparable to normal controls in terms of their surface marker (CD73, CD90 and CD105) expression and extent of suppression on proliferation of allogeneic T lymphocytes. In conclusion, MSCs from SLE demonstrated early signs of senescence which may be a corollary of active lupus or a contributory factor to disease pathogenesis. Lupus (2010) 19, 850-859.
引用
收藏
页码:850 / 859
页数:10
相关论文
共 36 条
  • [1] Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo
    Bartholomew, A
    Sturgeon, C
    Siatskas, M
    Ferrer, K
    McIntosh, K
    Patil, S
    Hardy, W
    Devine, S
    Ucker, D
    Deans, R
    Moseley, A
    Hoffman, R
    [J]. EXPERIMENTAL HEMATOLOGY, 2002, 30 (01) : 42 - 48
  • [2] Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion
    Baxter, MA
    Wynn, RF
    Jowitt, SN
    Wraith, JE
    Fairbairn, LJ
    Bellantuono, I
    [J]. STEM CELLS, 2004, 22 (05) : 675 - 682
  • [3] Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and auto-immune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro
    Bocelli-Tyndall, C.
    Bracci, L.
    Spagnoli, G.
    Braccini, A.
    Bouchenaki, M.
    Ceredig, R.
    Pistoia, V.
    Martin, I.
    Tyndall, A.
    [J]. RHEUMATOLOGY, 2007, 46 (03) : 403 - 408
  • [4] DERIVATION OF THE SLEDAI - A DISEASE-ACTIVITY INDEX FOR LUPUS PATIENTS
    BOMBARDIER, C
    GLADMAN, DD
    UROWITZ, MB
    CARON, D
    CHANG, CH
    [J]. ARTHRITIS AND RHEUMATISM, 1992, 35 (06): : 630 - 640
  • [5] Bruder SP, 1997, J CELL BIOCHEM, V64, P278, DOI 10.1002/(SICI)1097-4644(199702)64:2<278::AID-JCB11>3.0.CO
  • [6] 2-F
  • [7] Human Mesenchymal Stem Cells and Immunosuppressive Drug Interactions in Allogeneic Responses: An In Vitro Study Using Human Cells
    Buron, F.
    Perrin, H.
    Malcus, C.
    Hequet, O.
    Thaunat, O.
    Kholopp-Sarda, M. -N.
    Moulin, F. T.
    Morelon, E.
    [J]. TRANSPLANTATION PROCEEDINGS, 2009, 41 (08) : 3347 - 3352
  • [8] Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?
    Burt, RK
    Slavin, S
    Burns, WH
    Marmont, AM
    [J]. BLOOD, 2002, 99 (03) : 768 - 784
  • [9] Replacement of recipient stromal/mesenchymal cells after bone marrow transplantation using bone fragments and cultured osteoblast-like cells
    Cahill, RA
    Jones, OY
    Klemperer, M
    Steele, A
    Mueller, TO
    El-Badri, N
    Chang, Y
    Good, RA
    [J]. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2004, 10 (10) : 709 - 717
  • [10] Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells
    Colter, DC
    Sekiya, I
    Prockop, DJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (14) : 7841 - 7845