Effects of granulocyte colony-stimulating factor and stem cell factor, alone and in combination, on the biological behaviours of bone marrow mesenchymal stem cells


Aim: The effects of granulocyte colony- stimu-lating factor (G-CSF) and stem cell factor (SCF) on the proliferation and osteogenic differentia-tion capacity of bone marrow mesenchymal stem cells (MSCs) were studied in the experi-ment. Methods: Bone marrow MSCs were col-lected from rabbits successfully, and treated with various concentrations of G-CSF, SCF or a combination of the two. Flow cytometric ana-lyse, MTT test, CFU-F assay, and alkaline phosphatase (ALP) activity measurement were employed. Results: The results of flow cytome-try showed that immunophenotype of the cells were CD29+/CD45-, CD105+/ CD34–, CD90+/ HLADR–. MSCs were shown to constitutively express low levels of c-kit which could be en-hanced by SCF. G-CSF and SCF had an obvious facilitative effect on the proliferation of MSCs in a dose-dependent fashion. In addition, G-CSF and SCF would be effective in reversibly pre-venting their differentiation, as showed by the decrease of ALP activity, leading to self-renewal rather than differentiative cell divisions. The effects of G-CSF were superior to SCF. And cells in the group treated with combination of G-CSF and SCF showed more powerful effects than the groups treated with G-CS, SCF, or none of the two. Conclusion: On the whole, these studies demonstrated that MSCs responsed to G-CSF, SCF, and to G-CSF plus SCF in a manner that suppressed differentiation, and promotes proliferation and self-renewal, and support the view that these factors could act synergistically.

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Tang, F. , Wu, X. , Yu, X. , Yang, S. , Xu, W. and Li, J. (2009) Effects of granulocyte colony-stimulating factor and stem cell factor, alone and in combination, on the biological behaviours of bone marrow mesenchymal stem cells. Journal of Biomedical Science and Engineering, 2, 200-207. doi: 10.4236/jbise.2009.23033.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] P. Menasche Cell transplantation in myocardium. Ann Thorac Surg 2003, 75: S20-28.
[2] E. M. Horwitz, (2003) Bone marrow transplantation: It’s not just about blood anymore! Pediatr Transplant, 7, 56-58.
[3] N. Koike, D. Fukumura, O. Gralla, et al., (2004) Tissue engineering: Creation of long-lasting blood vessels, Nature, 428, 138-139.
[4] K. D. Lee, T. K. Kuo, J. Whang-Peng, et al., (2004) In vitro hepatic differentiation of human mesenchymal stem cells, Hepatology, 40, 1275-1284.
[5] D. Baksh, L. Song, and R. S. Tuan, (2004) Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy, J Cell Mol Med, 8, 301-316.
[6] A. Peister, J. A. Mellad, B. L. Larson, B. M. Hall, L. F. Gibson, and D. J. Prockop, (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.
[7] B. Short, N. Brouard, T. Occhiodoro-Scott, A. Ramakrishnan, and P. J. Simmons, (2003) Mesenchymal stem cells, Arch. Med. Res, 34, 565-571.
[8] V. Gangji, J. P. Hauzeur, C. Matos, V. De Maertelaer, M. Toungouz, and M. Lambermont, (2004) Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells: A pilot study, J Bone Joint Surg (Am), 86, 1153-1160.
[9] V. Gangji, J. P. Hauzeur, A. Schoutens, M. Hinsenkamp, T. Appelboom, and D. Egrise, (2003) Abnormalities in the replicative capacity of Osteoblastic cells in the proximal femur of patients with osteonecrosis of the femoral head, J Rheumatol, 30, 348-351.
[10] D. Orlic, J. M. Hill, and A. E. Arai, (2002) Stem cells for myocardial regeneration, Circ Res, 91, 1092-1102.
[11] M. K. Majumdar, M. A. Thiede, S. E. Haynesworth, S. P. Bruder, and S. L. Gerson, (2000) Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages, J Hematother Stem Cell Res, 9, 841-848.
[12] R. F. Duarte and D. A. Frank, (2000) SCF and G-CSF lead to the synergistic induction of proliferation and gene expression through complementary signaling pathways, Blood, 96, 3422-3430.
[13] R. Cancedda, G. Bianchi, A. Derubeis, and R. Quarto, (2003) Cell therapy for bone disease: A review of current status, Stem Cells, 21, 610-619.
[14] F. R. Rose and R. O. Oreffo, (2002) Bone tissue engineering: Hope vs hype, Biochem. Biophys. Res Commun., 292, 1-7.
[15] X. B. Yang, H. I. Roach, N. M. Clarke, et al., (2001) Human osteoprogenitor growth and differentiation on synthetic biodegradable structures after surface modification, Bone, 29, 523-531.
[16] D. C. Colter, I. Sekiya, D. J. Prockop, (2001) Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells, Proc Natl Acad Sci U S A, 98, 7841-7845.
[17] S. A. Wexler, C. Donaldson, P. Denning-Kendall, C. Rice, B. Bradley, and J. M. Hows, (2003) Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not, British Journal of Haematology, 121, 368-374.
[18] M. F. Pittenger, A. M. Mackay, S. C. Beck, et al., (1999) Multilineage potential of adult human mesenchymal stem cells, Science, 284, 143-147.
[19] A. P. Croff and S. A. Przyborski, (2004) Generation of neuroprogenitor-like cells from adult mammalian bone marrow stromal cells in vitro, Stem Cells Dev, 13, 409-420.
[20] Y. Jiang, B. N. Jahagirdar, R. L. Reinhardt, et al., (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418, 41-49.
[21] M. Studeny, F. C. Marini, R. E. Champlin, et al., (2002) Bone marrow-derived mesenchymal stem cells as vehicles for interferon-β delivery into tumours, Cancer Res, 62, 3603-3608.
[22] O. N. Koc, S. L. Gerson, B. W. Cooper, et al., (2000) 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, 18, 307-316.
[23] D. Orlic, J. Kajstura, S. Chimenti, et al., (2001) Bone marrow cells regenerate infarcted myocardium, Nature, 410, 701-705.
[24] M. Krampera, S. Glennie, R. Laylor, et al., (2003) Bone marrow mesenchymal stem cells inhibit the response of na?ve and memory antigen-specific T cells to their cognate peptide, Blood, 101, 3722-3729.
[25] B. Avalos, (1996) Molecular analysis of the granulocyte-colony stimulating factor receptor, Blood, 88, 761-777.
[26] M. L. McLemore, S. Grewal, F. Liu, et al., (2001) STAT-3 activation is required for normal G-CSF-dependent proliferation and granulocytic differentiation, Immunity, 14, 193-204.
[27] J. R. Fu, W. L. Liu, J. F. Zhou, et al., (2006) Sonichedgehog protein promotes bone marrow-derived endo- thelial progenitor cell proliferation, migration and VEGF production via PI 3- kinase/Akt signaling pathways, Acta Pharmacol Sin, 27, 685-693.
[28] O. Kollet, A. Spiegel, A. Peled, et al., (2001) Rapid and efficient homing of human CD34 (+) CD38 (-/low) CXCR4 (+) stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null) mice, Blood, 97, 3283-3291.
[29] B. Heissig, K. Hattori, and S. Dias, (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand, Cell, 109, 625-637.
[30] D. M. Bodine, N. E. Seidel, and D. Orlic, (1996) Bone marrow collected 14 days after in vivo administration of granulocyte colony- stimulating factor and stem cell factor to mice has 10-fold more repopulating ability than untreated bone marrow, Blood, 88, 89-97.
[31] E. H. Javazon, K. J. Beggs, and A. W. Flake, (2004) Mesenchymal stem cells: Paradoxes of passaging, Exp Hematol, 32, 414-425.
[32] P. A. Zuk, M. Zhu, H. Mizuno, et al., (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies, Tissue Eng, 7, 211-228.
[33] M. F. Pittenger and B. J. Martin, (2004) Mesenchymal stem cells and their potential as cardiac therapeutics, Circ Res, 95, 9-20.
[34] J. R. Smith, R. Pochampally, A. Perry, et al., (2004) Isolation of a highly clonogenic and multipotential subfraction of adult stem cells from bone marrow stroma, Stem Cells, 22, 823-831.

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