Characteristics of bone marrow stromal cells in mixed lymphocytes culture response

Abstract

At present more and more attention has been given to stromal cells of bone marrow (BMSCs) due to the possibility of using them as immunomodulators in clinical practice. Some investigators have noticed suppressive effect of bone marrow stromal cells on lymphocytes proliferation in mixed cultures. Properties of allogenous and syngeneic BMSCs in vitro have been studied. BMSCs influence on lymphocytes proliferation was assessed by the lymphocytes mixed culture response, the results were visualized with immune cytochemic staining of cells in S-phase on Bromdesoxiuridin (BrdU) inclusion. Bone marrow stromal cells, spleenocytes, and fibroblasts were obtained from Wistar rats and outbred rats. Both allogenic and syngeneic bone marrow stromal cells have not been shown to suppress lymphocytes proliferation. Moreover, allogenous BMSCs stimulate lymphocytes proliferation both in lymphocytes mixed culture response and in co-culturing. At the same time, proliferation of lymphocytes in response to allogenous BMSCs reaches 85% in BMSCs high concentrations, that is relevantly more than proliferation of lymphocytes in response to allogenous fibroblasts. It has been stated that supernatants of BMSCs cultures produce proliferation of lymphocytes as well.

Keywords

bone marrow stromal cells / lymphocytes mixed culture response

References

[1] Pittenger M.F., Mackay A.M., Beck S.C. Multilineage potential of human mesenchymal stem cells. Science 1999; 284: 143-7.

[2] Сергеев В.С. Иммунологические свойства мезенхимальных стромальных клеток. Клеточная трансплантология и тканевая инженерия 2005; 2: 39-42.

[3] Di Nicola M., Carlostella C., Magni M. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecifc mitogenic stimuli. Blood 2002; 99: 3838-43.

[4] Krampera M., Glennie S., Dyson J. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003; 101: 3722-9.

[5] Le Blanc K., Tammik C., Güherstürm C. et al. HLA-expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp. Hematol. 2003; 31: 890-6.

[6] Maitra B., Szekely E., Gjini K. Human mesenchymal stem cells support unrelated donor haematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant. 2004; 33: 597-604.

[7] Tse W.T., Pendleton J.D., Beyer W.M. et al. Suppression of allogeneic T- cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003; 75: 389-97.

[8] Kraitchman D.L., Tatsumi M., Gilson W.D. Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 2005; 112(10): 1451-61.

[9] Makkar R.R., Price M.J., Lill M. Intramyocardial injection of allogeneic bone marrow-derived mesenchymal stem cells without immunosuppression preserves cardiac function in a porcine model of myocardial infarction. J. Cardiovasc. Pharmacol. Ther. 2005; 10(4): 225-33.

[10] Dai W., Hale S.L., Martin B.J. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation 2005; 112(2): 214-23.

[11] Aggarwal S., Pittenger F. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105: 1815-22.

[12] Rasmusson I., Ringden O., Sundberg B., Le Blanc K. Mesenchymal stem cells inhibit lymphocyte activation by mitogens and allogens by different mechanisms. Exp. Cell. Res. In press.

[13] Nauta A.J., Westerhuis G., Kruisselbrink A.B. et al. Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. Blood 2005; 11.

[14] Coyne T.M., Akiva M., Woodbury D. et al. Marrow Stromal Cells Transplanted to the Adult Brain are Rejected by an Inflammatory Response and Transfer Donor Labels to Host Neurons and Glia. http://stemcells. alphamedpress.org/cgi/reprint/24/11/2483?maxtoshow=&HITS=10&hits =10&RESULTFORMAT=&author1 =Coyne%2C+TM&searchid=1 &FIRSTINDEX= 0&sortspec=relevance&resourcetype=HWCIT .

[15] Report of the AVMA Panel on Euthanasia. JAVMA 2001 ; 218(5): 669-96.

[16] Augello A., Tasso R., Negrini S.M. et al. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur. J. Immunol. 2005; 35: 1482-90.

[17] Di Nicola M., Carlostella C., Magni M. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecifc mitogenic stimuli. Blood 2002; 99: 3838-43.

[18] Djouad F., Plence P., Bony C. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003; 102: 3837-44.

[19] Güherstürm C., Ringdün O., Tammik C. et al. Immunological properties of human fetal mesenchymal stem cells. Am. J. Obstet. Gynecol. 2004; 190: 239-45.

[20] Toksoz D., Zsebo K., Smith K. Support of human hematopoiesis in long term bone marrow cultures by murine stromal cells selectively expressing the membrane bound and secreted forms of the human homologue of the steel gene product, stem cell factor. Proc. Natl. Acad. Sci. USA. 1992; 89: 7350-4.

[21] Güherstürm C., Ringdün O., Westgren M. et al. Immunomodulatory effects of human foetal liverderived mesenchymal stem cells. Bone Marrow Transplant. 2003; 32: 265-72.

[22] Rasmusson I., Ringdün O., Sundberg B., Le Blanc K. Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation 2003; 76: 1208-13.

[23] Wang J.W., Liu Y.B., Xu B. The study on immunomodulation of donor mesenchymal stem cells on discordant liver xenotransplantation. Zhonghua Wai Ke Za Zhi. 2005; 43(19): 1254 -8.

[24] Wang Y., Huso D., Harrington J. Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture. Cytotherapy 2005; 7(6): 509-19.

[25] Zhang Y. Z., Fouillard L., Chapel A. et al. Mesenchymal stem cells from human proximal femurs possess immunosupressive activity. Zhonghua Yi Xue Za Zhi. 2005; 85(39).

RIGHTS & PERMISSIONS

Eco-Vector