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Infusion of Endothelial Progenitor Cells Accelerates Hematopoietic and Immune Reconstitution, and Ameliorates the Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation

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Abstract

Hematopoietic stem cells transplantation (HSCT) causes endothelial cell damage, disrupting hematopoietic microenviroment and leading to various complications. We hypothesized that infusion of endothelial progenitor cells (EPCs) may improve endothelium repair, facilitate hematopoietic reconstitution, and alleviate complications associated with HSCT. C57Bl6, and BALB/c mice received total body irradiation followed by infusion of C57Bl6-derived bone marrow (BM) cells, with or without concomitant infusion of C57Bl6-derived EPCs. The time course of hematopoietic and immune reconstitution and the severity of the graft-versus-host disease (GVHD) were monitored. Further, to confirm that EPCs promote endothelial cell recovery, HSCT mice were treated with anti-VE-cadherin antibody targeting the endothelium. The EPCs-treated mice exhibited accelerated recovery of BM vasculature, cellularity, hematopoietic stem and progenitor cell recovery, improved counts of lymphocyte subsets in peripheral blood, and facilitated spleen structure reconstruction. EPCs infusion also ameliorated the GVHD in the C57Bl6 → BALB/c allo-HSCT model. Systemic administration of anti-VE-cadherin antibody significantly delayed hematological and immune reconstitution in the EPCs-infused mice. In conclusion, our data demonstrate that infusion of EPCs augments the hematopoietic and immune reconstitution, and alleviates the GVHD. These findings further highlight the relationship between the microvascular recovery, hematopoietic and immune reconstitution, and the GVHD.

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References

  1. Powles, R. (2010). 50 years of allogeneic bone-marrow transplantation. Lancet Oncology, 11, 305–306.

    Article  PubMed  Google Scholar 

  2. Richardson, P., & Guinan, E. (2001). Hepatic veno-occlusive disease following hematopoietic stem cell transplantation. Acta Haematologica, 106, 57–68.

    Article  PubMed  CAS  Google Scholar 

  3. Cahill, R. A., Spitzer, T. R., & Mazumder, A. (1996). Marrow engraftment and clinical manifestations of capillary leak syndrome. Bone Marrow Transplantation, 18, 177–184.

    PubMed  CAS  Google Scholar 

  4. Chute, J. P., Muramoto, G. G., Salter, A. B., Meadows, S. K., Rickman, D. W., Chen, B., et al. (2007). Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice. Blood, 109, 2365–2372.

    Article  PubMed  CAS  Google Scholar 

  5. Zeng, L., Yan, Z., Wang, L., Du, B., Pan, X., & Xu, K. (2008). Irradiation is an early determinant of endothelial injury during hematopoietic stem cell transplantation. Transplantation Proceedings, 40, 2661–2664.

    Article  PubMed  CAS  Google Scholar 

  6. Kopp, H. G., Avecilla, S. T., Hooper, A. T., Shmelkov, S. V., Ramos, C. A., Zhang, F., et al. (2005). Tie2 activation contributes to hemangiogenic regeneration after myelosuppression. Blood, 106, 505–513.

    Article  PubMed  CAS  Google Scholar 

  7. Zeng, L., Yan, Z., Ding, S., Xu, K., & Wang, L. (2008). Endothelial injury, an intriguing effect of methotrexate and cyclophosphamide during hematopoietic stem cell transplantation in mice. Transplantation Proceedings, 40, 2670–2673.

    Article  PubMed  CAS  Google Scholar 

  8. Kiel, M. J., & Morrison, S. J. (2006). Maintaining hematopoietic stem cells in the vascular niche. Immunity, 25, 862–864.

    Article  PubMed  CAS  Google Scholar 

  9. Tichelli, A., & Gratwohl, A. (2008). Vascular endothelium as ‘novel’ target of graft-versus-host disease. Best Practice and Research Clinical Haematology, 21, 139–148.

    Article  PubMed  CAS  Google Scholar 

  10. Woywodt, A., Scheer, J., Hambach, L., Buchholz, S., Ganser, A., Haller, H., et al. (2004). Circulating endothelial cells as a marker of endothelial damage in allogeneic hematopoietic stem cell transplantation. Blood, 103, 3603–3605.

    Article  PubMed  CAS  Google Scholar 

  11. Biedermann, B. C., Sahner, S., Gregor, M., Tsakiris, D. A., Jeanneret, C., Pober, J. S., et al. (2002). Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease. Lancet, 359, 2078–2083.

    Article  PubMed  Google Scholar 

  12. Hooper, A. T., Butler, J. M., Nolan, D. J., Kranz, A., Iida, K., Kobayashi, M., et al. (2009). Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells. Cell Stem Cell, 4, 263–274.

    Article  PubMed  CAS  Google Scholar 

  13. Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., et al. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275, 964–967.

    Article  PubMed  CAS  Google Scholar 

  14. Yoder, M. C., Mead, L. E., Prater, D., Krier, T. R., Mroueh, K. N., Li, F., et al. (2007). Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood, 109, 1801–1809.

    Article  PubMed  CAS  Google Scholar 

  15. Maltais, S., Perrault, L. P., & Ly, H. Q. (2011). The bone marrow-cardiac axis: role of endothelial progenitor cells in heart failure. European Journal of Cardio-Thoracic Surgery, 39, 368–374.

    Article  PubMed  Google Scholar 

  16. Patel, S. D., Waltham, M., Wadoodi, A., Burnand, K. G., & Smith, A. (2010). The role of endothelial cells and their progenitors in intimal hyperplasia. Therapeutic Advances in Cardiovascular Disease, 4, 129–141.

    Article  PubMed  CAS  Google Scholar 

  17. Lei, Z., Shi, H. L., Li, L., Tao, Y. G., Yong, L. W., Senga, H., et al. (2011). Batroxobin mobilizes circulating endothelial progenitor cells in patients with deep vein thrombosis. Clinical and Applied Thrombosis/Hemostasis, 17, 75–79.

    Article  CAS  Google Scholar 

  18. Salter, A. B., Meadows, S. K., Muramoto, G. G., Himburg, H., Doan, P., Daher, P., et al. (2009). Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivo. Blood, 113, 2104–2107.

    Article  PubMed  CAS  Google Scholar 

  19. Cooke, K. R., Kobzik, L., Martin, T. R., Brewer, J., Delmonte, J, Jr, Crawford, J. M., et al. (1996). An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. The roles of minor H antigens and endotoxin. Blood, 88, 3230–3239.

    PubMed  CAS  Google Scholar 

  20. Kaplan, D. H., Anderson, B. E., McNiff, J. M., Jain, D., Shlomchik, M. J., & Shlomchik, W. D. (2004). Target antigens determine graft-versus-host disease phenotype. Journal of Immunology, 173, 5467–5475.

    CAS  Google Scholar 

  21. Zeng, L., Ding, S., Yan, Z., Chen, C., Sang, W., Cao, J., et al. (2012). Irradiation induces homing of donor endothelial progenitor cells in allogeneic hematopoietic stem cell transplantation. International Journal of Hematology, 95, 189–197.

    Article  PubMed  Google Scholar 

  22. Zhang, J., Niu, C., Ye, L., Huang, H., He, X., Tong, W. G., et al. (2003). Identification of the haematopoietic stem cell niche and control of the niche size. Nature, 425, 836–841.

    Article  PubMed  CAS  Google Scholar 

  23. Kiel, M. J., Yilmaz, O. H., Iwashita, T., Yilmaz, O. H., Terhorst, C., & Morrison, S. J. (2005). SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell, 121, 1109–1121.

    Article  PubMed  CAS  Google Scholar 

  24. Chao, N. J., & Chen, B. J. (2006). Prophylaxis and treatment of acute graft-versus-host disease. Seminars in Hematology, 43, 32–41.

    Article  PubMed  CAS  Google Scholar 

  25. Bacigalupo, A., & Palandri, F. (2004). Management of acute graft versus host disease (GVHD). Hematology Journal, 5, 189–196.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Ms. Wenyuan Lin, Xuzhou Medical College, for excellent technical assistance. This work was supported in part by the National Basic Research Program (973), project grant 2009CB522400 (Y.L), and the National Natural Science Foundation of China, grants 30971281 (K.X), 81070446 (L.Z.) and 81000210 (C.C).

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Authors and Affiliations

  1. Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China

    Lingyu Zeng, Chong Chen, Zhiling Yan, Shuang Ding, Jiang Cao, Wei Chen, Hai Cheng, Zhenyu Li, Wei Sang, Lin Wang & Kailin Xu

  2. Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China

    Lingyu Zeng, Guoliang Song, Shijuan Xu, Lu Jia & Kailin Xu

  3. Laboratory of Transplant Immunology, West China Hospital, Sichuan University, No. 37 Wainanguoxue Street, Chengdu, 610041, Sichuan, China

    Lingyu Zeng & Youping Li

  4. Department of Hematology, Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    Chong Chen, Jiang Cao, Wei Chen & Kailin Xu

Authors
  1. Lingyu Zeng
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  2. Chong Chen
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  3. Guoliang Song
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  4. Zhiling Yan
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  5. Shijuan Xu
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  6. Lu Jia
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  7. Shuang Ding
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  8. Jiang Cao
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  9. Wei Chen
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  10. Hai Cheng
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  11. Zhenyu Li
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  12. Wei Sang
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  13. Lin Wang
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  14. Youping Li
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  15. Kailin Xu
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Corresponding authors

Correspondence to Youping Li or Kailin Xu.

Additional information

Lingyu Zeng and Chong Chen contributed equally to this study.

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Zeng, L., Chen, C., Song, G. et al. Infusion of Endothelial Progenitor Cells Accelerates Hematopoietic and Immune Reconstitution, and Ameliorates the Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation. Cell Biochem Biophys 64, 213–222 (2012). https://doi.org/10.1007/s12013-012-9387-5

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  • DOI: https://doi.org/10.1007/s12013-012-9387-5

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