Abstract
The mouse is a suitable experimental model to study the biology of mesenchymal stem cells (MSCs), as well as to be used in biocompatibility studies and tissue engineering models. However, the isolation and purification of murine MSCs is far more challenging than their counterparts from other species. In this study, we isolated, expanded and characterized mouse MSCs from bone marrow (BM-MSCs). Additionally, we analyzed the effects of two regulatory molecules, interleukin 17 (IL-17) and basic fibroblast growth factor (bFGF), on BM-MSCs growth and elucidated the signaling pathways involved. The results revealed that IL-17 increased the frequency of colony-forming units fibroblast (CFU-F) as well as the BM-MSCs proliferation in a dose-dependent manner, while bFGF supplementation had no significant effect on CFU-F frequency but induced an increase in cell proliferation. Their combined usage did not produce additive effects on BM-MSCs proliferation and even induced reduction in the number of CFU-F. Also, the involvement of both p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases (MAPKs) signaling in proliferative activity of IL-17 and bFGF on murine BM-MSCs and, moreover, the increased co-activation of a common signaling molecule, p38 MAPK, were demonstrated. Together, the data presented highlighted the role of IL-17 and bFGF in murine BM-MSCs proliferation and pointed to the complexity and specificity of the signaling networks leading to MSCs proliferation in response to different regulatory molecules.
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Bianchi G, Banfi A, Mastrogiacomo M, Notaro R, Luzzatto L, Cancedda R, Quarto R (2003) Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2. Exp Cell Res 287:98–105
Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology and potential application. Stem Cells 19:180–192
Bugarski D, Krstic A, Mojsilovic S, Vlaski M, Petakov M, Jovcic G, Stojanovic N, Milenkovic P (2007) Signaling pathways implicated in hematopoietic progenitor cell proliferation and differentiation. Exp Biol Med 232:156–163
Cárcamo-Orive I, Tejados N, Delgado J, Gaztelumendi A, Otaegui D, Lang V, Trigueros C (2008) ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential. Exp Cell Res 314:1777–1788
Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28:875–884
Digirolamo CM, Stokes D, Colter D, Phinney DG, Class R, Prockop DJ (1999) Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol 107:275–281
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Dj P, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 8:315–317
Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–247
Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luriá EA, Ruadkow IA (1974) Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp Hematol 2:83–92
Friedenstein AJ, Gorskaja JF, Kulagina NN (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 4:267–274
Garcia-Maya M, Anderson AA, Kendal CE, Kenny AV, Edwards-Ingram LC, Holladay A, Saffell JL (2006) Ligand concentration is a driver of divergent signaling and pleiotropic cellular responses to FGF. J Cell Physiol 206:386–393
Hirata T, Osuga Y, Hamasaki K, Yoshino O, Ito M, Hasegawa A et al (2008) Interleukin (IL)-17A stimulates IL-8 secretion, cyclooxygensase-2 expression, and cell proliferation of endometriotic stromal cells. Endocrinology 149:1260–1267
Huang W, La Russa V, Alzoubi A, Schwarzenberger P (2006) Interleukin-17A: a T-cell-derived growth factor for murine and human mesenchymal stem cells. Stem Cells 24:1512–1518
Huang H, Kim HJ, Chang EJ, Lee ZH, Hwang SJ, Kim HM, Lee Y, Kim HH (2009) IL-17 stimulates the proliferation and differentiation of human mesenchymal stem cells: implications for bone remodeling. Cell Death Differ 16:1332–1343
Inoue D, Numasaki M, Watanabe M, Kubo H, Sasaki T, Yasuda H et al (2006) IL-17A promotes the growth of airway epithelial cells through ERK-dependent signaling pathway. Biochem Biophys Res Commun 347:852–858
Krstić A, Ilić V, Mojsilović S, Jovcić G, Milenković P, Bugarski D (2009) p38 MAPK signaling mediates IL-17-induced nitric oxide synthase expression in bone marrow cells. Growth Factors 27:79–90
Lee SJ, Lee EJ, Kim SH, Choi I, Lee DM, Lee HJ, Yoon D, Chun T (2011) IL-17A promotes transdifferentiation of mouse myoblast cells (C2C12) into adipocytes by increasing the expression of peroxisome proliferator-activated receptor γ through CAAT/enhancer binding protein β signaling. Biotechnol Lett 33:229–235
Levy O, Dvir T, Tsur-Gang O, Granot Y, Cohen S (2008) Signal transducer and activator of transcription 3-A key molecular switch for human mesenchymal stem cell proliferation. Int J Biochem Cell Biol 40:2606–2618
Maher P (1999) p38 mitogen-activated protein kinase activation is required for fibroblast growth factor-2-stimulated cell proliferation but not differentiation. J Biol Chem 274:17491–17498
Miljkovic D, Trajkovic V (2004) Inducible nitric oxide synthase activation by interleukin-17. Cytokine Growth Factor Rev 15:21–32
Nadri S, Soleimani M, Hosseini RH, Massumi M, Atashi A, Izadpanan R (2007) An efficient method for isolation of murine bone marrow mesenchymal stem cells. Int J Dev Biol 51:723–729
Owen M (1988) Marrow stromal stem cells. J Cell Sci Suppl 10:63–76
Pappu R, Ramirez-Carrozzi V, Ota N, Ouyang W, Hu Y (2010) The IL-17 family cytokines in immunity and disease. J Clin Immunol 30:185–195
Peister A, Mellad JA, Larson BL, Hall BM, Gibson LF, Prockop DJ (2004) Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential. Blood 103:1662–1668
Phinney DG, Kopen G, Isaacson RL, Prockop DJ (1999) Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: variations in yield, growth, and differentiation. J Cell Biochem 72:570–585
Salem HK, Thiemermann C (2010) Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28:585–596
Shin JH, Shin DW, Noh M (2009) Interleukin-17A inhibits adipocyte differentiation in human mesenchymal stem cells and regulates pro-inflammatory responses in adipocytes. Biochem Pharmacol 77:1835–1844
Silva WA Jr, Covas DT, Panepucci RA, Proto-Siqueira R, Siufi JL, Zanette DL, Santos AR, Zago MA (2003) The profile of gene expression of human marrow mesenchymal stem cells. Stem Cells 21:661–669
Solchaga LA, Penick K, Porter JD, Goldberg VM, Caplan AI, Welter JF (2005) FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J Cell Physiol 203:398–409
Sotiropoulou PA, Perez SA, Salagianni M, Baxevanis CN, Papamichail M (2006) Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells 24:462–471
Sung JH, Yang HM, Park JB, Choi GS, Joh JW, Kwon CH, Chun JM, Lee SK, Kim SJ (2008) Isolation and characterization of mouse mesenchymal stem cells. Transplant Proc 40:2649–2654
Tropel P, Noël D, Platet N, Legrand P, Benabid AL, Berger F (2004) Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res 295:395–406
Villar V, Kocic J, Bugarski D, Jovcic G, Santibanez JF (2010) SKIP is required for TGF-β1-induced epithelial mesenchymal transition and migration in transformed keratinocytes. FEBS Lett 584:4586–4592
Zhou FH, Foster BK, Zhou XF, Cowin AJ, Xian CJ (2006) TNF-alpha mediates p38 MAP kinase activation and negatively regulates bone formation at the injured growth plate in rats. J Bone Miner Res 21:1075–1088
Acknowledgement
The excellent technical assistance of Mrs S. Marković is appreciated. This work was supported by a grant (#175062) from the Ministry of Education and Science, Republic of Serbia.
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Mojsilović, S., Krstić, A., Ilić, V. et al. IL-17 and FGF signaling involved in mouse mesenchymal stem cell proliferation. Cell Tissue Res 346, 305–316 (2011). https://doi.org/10.1007/s00441-011-1284-5
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DOI: https://doi.org/10.1007/s00441-011-1284-5