Abstract
Multipotent mesenchymal stem cells (MSCs) hold great promise in regenerative medicine, but one of the biggest challenges facing for their application is the ex vivo expansion to obtain enough undifferentiated cells. Fetal bovine serum (FBS), which can elicit possible contaminations of prion, virus, zoonosis or immunological reaction against xenogenic serum antigens, still remains essential to the culture formulations. There is an urgent need to identify potential factors for the undifferentiated expansion of MSCs to reduce the use of FBS or eventually replace it. A previously recognized housekeeping gene, β2-microglobulin (β2M), is demonstrated to act as a novel growth factor to stimulate the undifferentiated ex vivo expansion and preserve the pluripotency of adult MSCs from various sources. The use of β2M might have promising implications for future clinical application of MSCs.
Similar content being viewed by others
References
Balint E, Sprague SM (2001) Beta(2)-microglobulin and bone cell metabolism. Nephrol Dial Transplant 16:108–111
Canalis E, McCarthy T, Centrella M (1987) A bone-derived growth factor isolated from rat is β2-microglobulin. Endocrinology 121:1198–1200
Chen FH, Tuan RS (2008) Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther 10(5):223
Evans DB, Thavarajan M, Kanis JA (1991) Immunoreactivity and proliferative actions of β2-microglobulin on human bone derived cells in vitro. Biochem Biophys Res Commun 175:795–803
Horwitz EM (2004) Dkk-1-mediated expansion of adult stem cells. Trends Biotechnol 22(8):386–388
Huang WC, Wu D, Xie Z et al (2006) Beta2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis. Cancer Res 66:9108–9116
Mannello F, Tonti GA (2007) Concise review: no breakthroughs for human mesenchymal and embryonic stem cell culture: conditioned medium, feeder layer, or feeder-free; medium with fetal calf serum, human serum, or enriched plasma; serum-free, serum replacement nonconditioned medium, or ad hoc formula? All that glitters is not gold!. Stem Cells 25(7):1603–1609
Menaa C, Esser E, Sprague SM (2008) Beta2-microglobulin stimulates osteoclast formation. Kidney Int 273:1275–1281
Min R, Li Z, Epstein J et al (2002) β2-microglobulin as a negative growth regulator of myeloma cells. Br J Haematol 118:495–505
Nomura T, Huang WC, Zhau HE et al (2006) Beta2-microglobulin promotes the growth of human renal cell carcinoma through the activation of the protein kinase A, cyclic AMP-responsive element-binding protein, and vascular endothelial growth factor axis. Clin Cancer Res 12:7294–7305
Rowley DR, Dang TD, McBride L et al (1995) β2 microglobulin is mitogenic to PC-3 prostatic carcinoma cells and antagonistic to transforming growth factor β1 action. Cancer Res 55:781–786
Shi CM, Zhu Y, Huang WC et al (2007) Bi-directional interactions of bone marrow mesenchymal stem cells with human prostate cancer cells. J Urol 177(4 Suppl):92
Shi C, Zhu Y, Su Y, Chung LW, Cheng T (2009) Beta2-Microglobulin: emerging as a promising cancer therapeutic target. Drug Discov Today 14:25–30
Sotiropoulou PA, Perez SA, Salagianni M et al (2006) Cell culture medium composition and translational adult bone marrow-derived stem cell research. Stem Cells 24(5):1409–1410
Strominger JL (2002) Human histocompatibility proteins. Immunol Rev 185:69–77
Stute N, Holtz K, Bubenheim M et al (2004) Autologous serum for isolation and expansion of human mesenchymal stem cells for clinical use. Exp Hematol 32:1212–1225
Tamama K, Fan VH, Griffith LG et al (2006) Epidermal growth factor as a candidate for ex vivo expansion of bone marrow-derived mesenchymal stem cells. Stem Cells 24(3):686–695
Uccelli A, Moretta L, Pistoia V et al (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8:726–736
Xie J, Yi Q (2003) Beta2-microglobulin as a potential initiator of inflammatory responses. Trends Immunol 24:228–229
Xie J, Wang Y, Freeman ME et al (2003) Beta2-microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells. Blood 101(10):4005–4012
Yang J, Qian J, Wezeman M et al (2006) Targeting beta2-microglobulin for induction of tumor apoptosis in human hematological malignancies. Cancer Cell 10:295–307
Yang J, Zhang X, Wang J et al (2007) Anti beta2-microglobulin monoclonal antibodies induce apoptosis in myeloma cells by recruiting MHC class I to and excluding growth and survival cytokine receptors from lipid rafts. Blood 110:3028–3035
Zhu Y, Shi C (2008) Beta2-microglobulin, a novel factor for the expansion of mesenchymal stem cells. J Biotechnol 136(S):S177
Acknowledgements
This work is supported by the following grants from China: NKBRP2005CB522605, SKLZZ200810, NFSC30400188, FANEDD200777, IRT0712 and CSTC2008BB5023.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhu, Y., Su, Y., Cheng, T. et al. β2-Microglobulin as a potential factor for the expansion of mesenchymal stem cells. Biotechnol Lett 31, 1361–1365 (2009). https://doi.org/10.1007/s10529-009-0027-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-009-0027-0