The Study of Altered Immune Status of UCMSC upon the Activation of TLR1/2 Pathway

MA Yu, ZHANG Li, JIANG Ting. et al

Abstract

To study whether the activation of Toll like receptor 1/2 (TLR1/2) has influence on the immune status of umbilical cord mesenchymal stem cell (UCMSC). Methods TLR1/2 agonist Pam3CSK4 was conducted in UCMSC-peripheral blood mononuclear cell (PBMC) co-culture system. Flow cytometry and lactate dehydrogenase (LDH) detection were used to measure the proliferation of PBMC and immune attack of PBMC to UCMSC, respectively. The detection of expressions of co-stimulator and stem cell markers of UCMSC upon TLR1/2 activation was completed by flow cytometry. Real-time PCR was introduced to assay the expression of many immune-related molecules in UCMSC. Cell differentiation staining was conducted to study the change of differentiation ability of UCMSC. Results Activation of TLR1/2 pathway in UCMSC increased the proliferation of PBMC and attack of PBMC to UCMSC, but without influenced the expressions of co-stimulator and stem cell markers. The results of real-time PCR showed that many immune-related molecules were dramatically induced in UCMSC upon TLR1/2 activation, such as 〔interleukin (IL) -2,IL-6,IL-10,IL-12,interferon-γ (IFN-γ), nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α)〕. However, the activation of TLR1/2 had no influence on the differentiation ability of UCMSC. Conclusion Activation of TLR1/2 altered the immune status of UCMSC, including increase the immune attack to UCMSC.

 

Keywords: Umbilical cord mesenchymal stem cell, Toll like receptor 1/2 Immune-related molecules, Immune status 


Full Text:

PDF


References


Bassi E, Aita CA, Camara NO. Immune regulatory properties of multipotent mesenchymal stromal cells: where do we stand? World J Stem Cells,2011;3( 1) s 1-8.

Shi M, Liu ZW, Wang FS. Immunomodulatory properties and therapeutic application of mesenchymal stem cells. Clin Exp Immunol,2011; 164(1) ; 1-8.

Phinney IXJ, Prockop DJ. Concise review; mesenchymal stem/ multipotent stromal cells; the state of transdifferentiation and modes of tissue repair current views. Stem Cells, 2007; 25 (11);2896-2902.

Vojtassak J, Danisovic L, Kubes M, et al. Autologous biograft and mesenchymal stem cells in treatment of the diabetic foot. Neuro Endocrinol Lett, 2006 ; 27 ( Suppl 2) ; 134- 137.

Kharaziha P. Hellstrom PM, Noorinayer B, et al. Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection; a phase-Q clinical trials. Eur J Gastroenterol Hepatol.2009;21 (10): 1199-1205.

Sun L. Wang D, Liang J, et al. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum,2010;62(2) ;2467-2475.

Nauta AJ, Westerhuis G. Kruisselbrink AB, et al. Donor- derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. Blood.2011; 108(6);2114-2120.

Li Y. Lin F. Mesenchymal stem cells are injured by complement after their contact with serum. Blood, 2012; 120 (17);3436-3443.

Blasius AL, Beutler B. Intracellular toll-like receptors. Immunity,2010;32(3) :305-315.

DelaRosa O, Lombardo K. Modulation of adult mesenchymal stem cells activity by toll-like receptors: implications on therapeutic potential. Mediators Inflamm. 2010; 10 ( 2 ); 865- 601.

Zhang L, Liu D, Pu D. et al. The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells. Biol Res,2015;48(1) ;6. doi; 10.1186/0717-6287-48-6.

Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell.2006 ; 124(4 );783-801.

Pevsner-Fischer M, Morad V. Cohen-Sfady M,etul. Toll like receptors and their ligands control mesenchymal stem cell functions. Blood,2007; 109(4); 1422-1432.

Alaina BS, Chen BY. Marc LN.et al. Validation of the 2- calculation as alternate method of data analysis for quantitative PCRof BCR-ABL P210 transcripts. Diag Mol Path, 2006; 15 (1): 56-61.

VanPoll D. Parekkadan В. Cho CH-,et al. Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in -vivo. Hepatology, 2008; 47 (5):1634-1643.

Kong D, Zhuang X, Wang D, et al. Umbilical cord mesenchymal stem cells transfusion ameliorated hyperglycemia in patients with type 2 diabetes mellitus. Clin Lab, 2014; 60

(12):1969-1976.

Huang XP. Sun Z, Miyagi Y, et al. Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation.2010; 122(23) :2419-2429.

Tomchuck SL. Zwezdaryk KJ, Coffel SB, et al. Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells,2008; 26(1):99-107.


Refbacks

  • There are currently no refbacks.