Tumor Biology

, Volume 35, Issue 5, pp 4307–4316 | Cite as

Impaired osteogenic differentiation of mesenchymal stem cells derived from bone marrow of patients with lower-risk myelodysplastic syndromes

  • Chengming Fei
  • Youshan Zhao
  • Shucheng Gu
  • Juan Guo
  • Xi Zhang
  • Xiao Li
  • Chunkang Chang
Research Article


The pathogenesis of myelodysplastic syndromes (MDS) has not been completely understood, and insufficiency of the hematopoietic microenvironment can be an important factor. Mesenchymal stem cells (MSCs) and osteoblasts are key components of the hematopoietic microenvironment. Here, we measured the expression of multiple osteogenic genes in 58 MSCs from MDS patients with different disease stages and subtypes by real-time PCR and compared the osteogenic differentiation of MSCs from 20 MDS patients with those of MSCs from eight normal controls quantitatively and dynamically. The mRNA level of Osterix and RUNX2, two key factors involved in the early differentiation process toward osteoblasts, was significantly reduced in undifferentiated MSCs from lower-risk MDS. After osteogenic induction, lower-risk MDS showed lower alkaline phosphatase activity, less intense alizarin red S staining, and lower gene expression of osteogenic differentiation markers; however, higher-risk MDS was normal. Finally, in bone marrow biopsy, the number of osteoblasts was significantly decreased in lower-risk MDS. These results indicate that MSCs from lower-risk MDS have impaired osteogenic differentiation functions, suggesting their insufficient stromal support in MDS.


Mesenchymal stem cells Osteoblasts Osteogenic differentiation Myelodysplastic syndromes 



This study was supported by the National Natural Science Foundation of China (NNSFC81170463).

Conflicts of interest



  1. 1.
    Nimer SD. Myelodysplastic syndromes. Blood. 2008;111(10):4841–51.CrossRefPubMedGoogle Scholar
  2. 2.
    Tauro S, Hepburn MD, Peddie CM, et al. Functional disturbance of marrow stromal microenvironment in the myelodysplastic syndromes. Leukemia. 2002;16(5):785–90.CrossRefPubMedGoogle Scholar
  3. 3.
    Ishibashi M, Tamura H, Ogata K. Disease progression mechanism in myelodysplastic syndromes: insight into the role of the microenvironment. Leuk Res. 2011;35(11):1449–52.CrossRefPubMedGoogle Scholar
  4. 4.
    Muguruma Y, Yahata T, Miyatake H, et al. Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment. Blood. 2006;107(5):1878–87.CrossRefPubMedGoogle Scholar
  5. 5.
    Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425(6960):841–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Raaijmakers MHGP, Mukherjee S, Guo S, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464(7290):852–7.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Valent P, Horny HP, Bennett JM, et al. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res. 2007;31(6):727–36.CrossRefPubMedGoogle Scholar
  8. 8.
    Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100(7):2292–302.CrossRefPubMedGoogle Scholar
  9. 9.
    Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.PubMedGoogle Scholar
  10. 10.
    Lemischka IR, Moore KA. Stem cells: interactive niches. Nature. 2003;425(6960):778–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Moore KA, Lemischka IR. Stem cells and their niches. Science. 2006;311(5769):1880–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425(6960):836–41.CrossRefPubMedGoogle Scholar
  13. 13.
    Flores-Figueroa E, Montesinos JJ, Flores-Guzmán P, et al. Functional analysis of myelodysplastic syndromes-derived mesenchymal stem cells. Leuk Res. 2008;32(9):1407–16.CrossRefPubMedGoogle Scholar
  14. 14.
    Soenen-Cornu V, Tourino C, Bonnet ML, et al. Mesenchymal cells generated from patients with myelodysplastic syndromes are devoid of chromosomal clonal markers and support short-and long-term hematopoiesis in vitro. Oncogene. 2005;24(15):2441–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Varga G, Kiss J, Várkonyi J, et al. Inappropriate Notch activity and limited mesenchymal stem cell plasticity in the bone marrow of patients with myelodysplastic syndromes. Pathol Oncol Res. 2007;13(4):311–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Song LX, Guo J, He Q, et al. Bone marrow mesenchymal stem cells in myelodysplastic syndromes: cytogenetic characterization. Acta Haematol. 2012;128(3):170–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Ferrer RA, Wobus M, List C, et al. Mesenchymal stromal cells from patients with myelodysplastic syndrome display distinct functional alterations that are modulated by lenalidomide. Haematologica. 2013;98(11):1677–85.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Mellibovsky L, Diez A, Serrano S, et al. Bone remodeling alterations in myelodysplastic syndrome. Bone. 1996;19(4):401–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Chitteti BR, Cheng YH, Streicher DA, et al. Osteoblast lineage cells expressing high levels of Runx2 enhance hematopoietic progenitor cell proliferation and function. J cell biochem. 2010;111(2):284–94.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Aizawa S, Nakano M, Iwase O, et al. Bone marrow stroma from refractory anemia of myelodysplastic syndrome is defective in its ability to support normal CD34-positive cell proliferation and differentiation in vitro. Leuk Res. 1999;23(3):239–46.CrossRefPubMedGoogle Scholar
  21. 21.
    Tennant GB, Walsh V, Truran LN, et al. Abnormalities of adherent layers grown from bone marrow of patients with myelodysplasia. Br J haematol. 2000;111(3):853–62.PubMedGoogle Scholar
  22. 22.
    Zhao ZG, Xu W, Yu HP, et al. Functional characteristics of mesenchymal stem cells derived from bone marrow of patients with myelodysplastic syndromes. Cancer Lett. 2012;317(2):136–43.CrossRefPubMedGoogle Scholar
  23. 23.
    Lacey DC, Simmons PJ, Graves SE, et al. Proinflammatory cytokines inhibit osteogenic differentiation from stem cells: implications for bone repair during inflammation. Osteoarthritis Cartilage. 2009;17(6):735–42.CrossRefPubMedGoogle Scholar
  24. 24.
    Bellamy WT, Richter L, Sirjani D, et al. Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood. 2001;97(5):1427–34.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Chengming Fei
    • 1
  • Youshan Zhao
    • 1
  • Shucheng Gu
    • 1
  • Juan Guo
    • 1
  • Xi Zhang
    • 1
  • Xiao Li
    • 1
  • Chunkang Chang
    • 1
  1. 1.Department of HematologyShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina

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