Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus

Abstract

Bone marrow-derived mesenchymal stem cells (MSCs) are key components of the hematopoietic microenvironment and provide support to hematopoiesis and modulate immune system. Several studies suggest that SLE may be seen as stem cell disorders. However, it is unclear that whether MSCs from SLE patients are defective. So in this research, we studied the biological character of bone marrow derived MSCs in patients with SLE, focused on their phenotype (morphology and immunophenotype), karyotype, cytokines expression and hematopoietic support of MSCs. Our results showed that MSCs from SLE patients and normal controls can be successfully culture-expanded, but the MSCs from SLE grew more slowly than those of normal controls (P < 0.05). Cells from both groups were positive for CD29, CD44 and CD105, and negative for CD14, CD34, CD45 and HLADR. MSCs from SLE have a normal karyotype. Both groups express IL-6, IL7, IL-11, macrophage colony stimulating factor (M-CSF) and stem cell factor (SCF) at mRNA level. While IL-6 and IL-7 were down-regulated in MSCs from SLE patient (P < 0.05) at mRNA level. The MSCs from SLE patients and normal controls were infused into ICR (Tac: Icr: Ha strain) mice after high-dose chemotherapy, with no adverse events in either group. Recovery of white blood cells, hemoglobin and platelet was more rapid (P < 0.05) compared with the group without MSCs infusion. We conclude that MSCs in patient with SLE have abnormalities compared with those in normal control. MSCs in patient with SLE may play an important role in the SLE pathogenesis.

Keywords

biological character cytokine hematopoietic support mesenchymal stem cells systemic lupus erythematosus

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References

Friedenstein AJ , Petrakova KV , Kurolesova AI , Frolova GP . Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 1968; 6: 230–247.

Owen M . Marrow stromal stem cells. J Cell Sci Suppl 1988; 10: 63–76.

Di Nicola M , Carlo-Stella C , Magni M et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99: 3838–3843.

Djouad F , Plence P , Bony C et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003; 102: 3837–3844.

Tse WT , Pendleton JD , Beyer WM , Egalka MC , Guinan EC . Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003; 75: 389–397.

Le Blanc K , Rasmusson I , Sundberg B et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363: 1439–1441.

Bartholomew A , Sturgeon C , Siatskas M et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002; 30: 42–48.

Kim DH , Yoo KH , Choi KS et al. Gene expression profile of cytokine and growth factor during differentiation of bone marrow-derived mesenchymal stem cell. Cytokine 2005; 31: 119–126.

Ikehara S , Inaba M , Yasumizu R et al. Autoimmune diseases as stem cell disorders. Tohoku J Exp Med 1994; 173: 141–155.

10.

Hochberg MC . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725-1725.

11.

Schned ES , Glickstein SL , Doyle MA . Derivation of the SLEDAI. Arthritis Rheum 1993; 36: 877–878.

12.

Morton JI , Siegel BV . Transplantation of autoimmune potential. I. Development of antinuclear antibodies in H-2 histocompatible recipients of bone marrow from New Zealand Black mice. Proc Natl Acad Sci USA 1974; 71: 2162–2165.

13.

Ikehara S , Good RA , Nakamura T et al. Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci USA 1985; 82: 2483–2487.

14.

Koc ON , Peters C , Aubourg P et al. Bone marrow-derived mesenchymal stem cells remain host-derived despite successful hematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases. Exp Hematol 1999; 27: 1675–1681.

15.

Haynesworth SE , Baber MA , Caplan AI . Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies. Bone 1992; 13: 69–80.

16.

Bruder SP , Horowitz MC , Mosca JD , Haynesworth SE . Monoclonal antibodies reactive with human osteogenic cell surface antigens. Bone 1997; 21: 225–235.

17.

Lazzari L , Lucchi S , Rebulla P et al. Long-term expansion and maintenance of cord blood haematopoietic stem cells using thrombopoietin, Flt3-ligand, interleukin (IL)-6 and IL-11 in a serum-free and stroma-free culture system. Br J Haematol 2001; 112: 397–404.

18.

Biesecker LG , Emerson SG . Interleukin-6 is a component of human umbilical cord serum and stimulates hematopoiesis in embryonic stem cells in vitro. Exp Hematol 1993; 21: 774–778.

19.

Fry TJ , Mackall CL . The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance. J Immunol 2005; 174: 6571–6576.

20.

Armitage RJ , Namen AE , Sassenfeld HM , Grabstein KH . Regulation of human T cell proliferation by IL-7. J Immunol 1990; 144: 938–941.

21.

Koc ON , Gerson SL , Cooper BW et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 2000; 18: 307–316.

22.

Papadaki HA , Boumpas DT , Gibson FM et al. Increased apoptosis of bone marrow CD34(+) cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus. Br J Haematol 2001; 115: 167–174.