DOI QR코드

DOI QR Code

Mesenchymal Stem Cell Lines Isolated by Different Isolation Methods Show Variations in the Regulation of Graft-versus-host Disease

  • Yoo, Hyun Seung (Translational Research Center, Inha University School of Medicine) ;
  • Yi, TacGhee (Translational Research Center, Inha University School of Medicine) ;
  • Cho, Yun Kyoung (HomeoTherapy Co. Ltd.) ;
  • Kim, Woo Cheol (Department of Radiation Oncology, Inha University School of Medicine) ;
  • Song, Sun U. (Translational Research Center, Inha University School of Medicine) ;
  • Jeon, Myung-Shin (Translational Research Center, Inha University School of Medicine)
  • Received : 2013.06.26
  • Accepted : 2013.07.11
  • Published : 2013.08.30

Abstract

Since the discovery of the immunomodulation property of mesenchymal stem cells (MSCs) about a decade ago, it has been extensively investigated whether MSCs can be used for the treatment of immune-related diseases, such as graft versus-host disease (GvHD). However, how to evaluate the efficacy of human MSCs for the clinical trial is still unclear. We used an MHC-mismatched model of GvHD (B6 into BALB/c). Surprisingly, the administration of the human MSCs (hMSCs) could reduce the GvHD-related mortality of the mouse recipients and xenogeneically inhibit mouse T-cell proliferation and $IFN-{\gamma}$ production in vitro. We recently established a new protocol for the isolation of a homogeneous population of MSCs called subfractionation culturing methods (SCM), and established a library of clonal MSC lines. Therefore, we also investigated whether MSCs isolated by the conventional gradient centrifugation method (GCM) and SCM show different efficacy in vivo. Intriguingly, clonal hMSCs (hcMSCs) isolated by SCM showed better efficacy than hMSCs isolated by GCM. Based on these results, the MHC-mismatched model of GvHD may be useful for evaluating the efficacy of human MSCs before the clinical trial. The results of this study suggest that different MSC lines may show different efficacy in vivo and in vitro.

Keywords

References

  1. Goker, H., I. C. Haznedaroglu, and N. J. Chao. 2001. Acute graft-vs-host disease: pathobiology and management. Exp. Hematol. 29: 259-277. https://doi.org/10.1016/S0301-472X(00)00677-9
  2. Menillo, S. A., S. L. Goldberg, P. McKiernan, and A. L. Pecora. 2001. Intraoral psoralen ultraviolet A irradiation (PUVA) treatment of refractory oral chronic graft-versus-host disease following allogeneic stem cell transplantation. Bone Marrow. Transplant. 28: 807-808. https://doi.org/10.1038/sj.bmt.1703231
  3. Deeg, H. J. 2007. How I treat refractory acute GVHD. Blood 109: 4119-4126. https://doi.org/10.1182/blood-2006-12-041889
  4. Rager, A., N. Frey, S. C. Goldstein, R. Reshef, E. O. Hexner, A. Loren, S. M. Luger, A. Perl, D. Tsai, J. Davis, M. Vozniak, J. Smith, E. A. Stadtmauer, and D. L. Porter. 2011. Inflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD. Bone Marrow. Transplant. 46: 430-435. https://doi.org/10.1038/bmt.2010.117
  5. Schub, N., A. Gunther, A. Schrauder, A. Claviez, C. Ehlert, M. Gramatzki, and R. Repp. 2011. Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective. Bone Marrow. Transplant. 46: 143-147. https://doi.org/10.1038/bmt.2010.68
  6. Prockop, D. J. 1997. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276: 71-74. https://doi.org/10.1126/science.276.5309.71
  7. Branch, M. J., K. Hashmani, P. Dhillon, D. R. Jones, H. S. Dua, and A. Hopkinson. 2012. Mesenchymal stem cells in the human corneal limbal stroma. Invest. Ophthalmol. Vis. Sci. 53: 5109-5116. https://doi.org/10.1167/iovs.11-8673
  8. Tse, W. T., J. D. Pendleton, W. M. Beyer, M. C. Egalka, and E. C. Guinan. 2003. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 75: 389-397. https://doi.org/10.1097/01.TP.0000045055.63901.A9
  9. Di Nicola, M., C. Carlo-Stella, M. Magni, M. Milanesi, P. D. Longoni, P. Matteucci, S. Grisanti, and A. M. Gianni. 2002. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99: 3838-3843. https://doi.org/10.1182/blood.V99.10.3838
  10. Jiang, X. X., Y. Zhang, B. Liu, S. X. Zhang, Y. Wu, X. D. Yu, and N. Mao. 2005. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105: 4120-4126. https://doi.org/10.1182/blood-2004-02-0586
  11. Sotiropoulou, P. A., S. A. Perez, A. D. Gritzapis, C. N. Baxevanis, and M. Papamichail. 2006. Interactions between human mesenchymal stem cells and natural killer cells. Stem. Cells. 24: 74-85. https://doi.org/10.1634/stemcells.2004-0359
  12. Corcione, A., F. Benvenuto, E. Ferretti, D. Giunti, V. Cappiello, F. Cazzanti, M. Risso, F. Gualandi, G. L. Mancardi, V. Pistoia, and A. Uccelli. 2006. Human mesenchymal stem cells modulate B-cell functions. Blood 107: 367-372. https://doi.org/10.1182/blood-2005-07-2657
  13. Glennie, S., I. Soeiro, P. J. Dyson, E. W. Lam, and F. Dazzi. 2005. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 105: 2821-2827. https://doi.org/10.1182/blood-2004-09-3696
  14. Le Blanc, K., I. Rasmusson, B. Sundberg, C. Gotherstrom, M. Hassan, M. Uzunel, and O. Ringden. 2004. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 363: 1439-1441. https://doi.org/10.1016/S0140-6736(04)16104-7
  15. Le Blanc, K., F. Frassoni, L. Ball, F. Locatelli, H. Roelofs, I. Lewis, E. Lanino, B. Sundberg, M. E. Bernardo, M. Remberger, G. Dini, R. M. Egeler, A. Bacigalupo, W. Fibbe, and O. Ringden; Developmental Committee of the European Group for Blood and Marrow Transplantation. 2008. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 371: 1579- 1586. https://doi.org/10.1016/S0140-6736(08)60690-X
  16. Ringden, O., M. Uzunel, I. Rasmusson, M. Remberger, B. Sundberg, H. Lonnies, H. U. Marschall, A. Dlugosz, A. Szakos, Z. Hassan, B. Omazic, J. Aschan, L. Barkholt, and K. Le Blanc. 2006. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 81: 1390- 1397. https://doi.org/10.1097/01.tp.0000214462.63943.14
  17. Allison, M. 2009. Genzyme backs osiris, despite prochymal flop. Nat. Biotechnol. 27: 966-967. https://doi.org/10.1038/nbt1109-966
  18. Li, W. J., H. Chiang, T. F. Kuo, H. S. Lee, C. C. Jiang, and R. S. Tuan. 2009. Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study. J. Tissue. Eng. Regen. Med. 3: 1-10. https://doi.org/10.1002/term.127
  19. Liao, W., J. Xie, J. Zhong, Y. Liu, L. Du, B. Zhou, J. Xu, P. Liu, S. Yang, J. Wang, Z. Han, and Z. C. Han. 2009. Therapeutic effect of human umbilical cord multipotent mesenchymal stromal cells in a rat model of stroke. Transplantation 87: 350-359. https://doi.org/10.1097/TP.0b013e318195742e
  20. Yan, H. and C. Yu. 2007. Repair of full-thickness cartilage defects with cells of different origin in a rabbit model. Arthroscopy 23: 178-187. https://doi.org/10.1016/j.arthro.2006.09.005
  21. Bruck, F., L. Belle, C. Lechanteur, L. de Leval, M. Hannon, S. Dubois, E. Castermans, S. Humblet-Baron, S. Rahmouni, Y. Beguin, A. Briquet, and F. Baron. 2013. Impact of bone marrow-derived mesenchymal stromal cells on experimental xenogeneic graft-versus-host disease. Cytotherapy 15: 267-279 https://doi.org/10.1016/j.jcyt.2012.09.003
  22. Song, S. U., C. S. Kim, S. P. Yoon, S. K. Kim, M. H, Lee, J. S. Kang, G. S. Choi, S. H. Moon, M. S. Choi, Y. K. Cho, and B. K. Son. 2008. Variations of clonal marrow stem cell lines established from human bone marrow in surface epitopes, differentiation potential, gene expression, and cytokine secretion. Stem. Cells. Dev. 17: 451-461. https://doi.org/10.1089/scd.2007.0167
  23. Jeon, M. S., T. G. Yi, H. J. Lim, S. H. Moon, M. H. Lee, J. S. Kang, C. S. Kim, D. H. Lee, and S. U. Song. 2011. Characterization of mouse clonal mesenchymal stem cell lines established by subfractionation culturing method. World. J. Stem. Cells. 3: 70-82. https://doi.org/10.4252/wjsc.v3.i8.70
  24. Saito, T., J. Q. Kuang, B. Bittira, A. Al-Khaldi, and R. C. Chiu. 2002. Xenotransplant cardiac chimera: immune tolerance of adult stem cells. Ann. Thorac. Surg. 74: 19-24. https://doi.org/10.1016/S0003-4975(02)03591-9
  25. Liechty, K. W., T. C. MacKenzie, A. F. Shaaban, A. Radu, A. M. Moseley, R. Deans, D. R. Marshak, and A. W. Flake. 2000. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat. Med. 6: 1282-1286. https://doi.org/10.1038/81395
  26. Jeon, M. S., H. J. Lim, T. G. Yi, M. W. Im, H. S. Yoo, J. H. Choi, E. Y. Choi, and S. U. Song. 2010. Xenoreactivity of human clonal mesenchymal stem cells in a major histocompatibility complex-matched allogeneic graft-versus-host disease mouse model. Cell. Immunol. 261: 57-63. https://doi.org/10.1016/j.cellimm.2009.11.001
  27. Ren, G., L. Zhang, X. Zhao, G. Xu, Y. Zhang, A. I. Roberts, R. C. Zhao, and Y. Shi. 2008. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell. Stem. Cell. 2: 141-150. https://doi.org/10.1016/j.stem.2007.11.014
  28. Dazzi, F. and F. M. Marelli-Berg. 2008. Mesenchymal stem cells for graft-versus-host disease: close encounters with T cells. Eur. J. Immunol. 38: 1479-1482. https://doi.org/10.1002/eji.200838433
  29. Sato, K., K. Ozaki, I. Oh, A. Meguro, K. Hatanaka, T. Nagai, K. Muroi, and K. Ozawa. 2007. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 109: 228-234. https://doi.org/10.1182/blood-2006-02-002246
  30. Katz, J. B., A. J. Muller, and G. C. Prendergast. 2008. Indoleamine 2,3-dioxygenase in T-cell tolerance and tumoral immune escape. Immunol. Rev. 222: 206-221. https://doi.org/10.1111/j.1600-065X.2008.00610.x
  31. Baron, F. and R. Storb. 2012. Mesenchymal stromal cells: a new tool against graft-versus-host disease? Biol. Blood Marrow. Transplant. 18: 822-840. https://doi.org/10.1016/j.bbmt.2011.09.003
  32. Sudres, M., F. Norol, A. Trenado, S. Gregoire, F. Charlotte, B. Levacher, J. J. Lataillade, P. Bourin, X. Holy, J. P. Vernant, D. Klatzmann, and J. L. Cohen. 2006. Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J. Immunol. 176: 7761-7767. https://doi.org/10.4049/jimmunol.176.12.7761
  33. Polchert, D., J. Sobinsky, G. Douglas, M. Kidd, A. Moadsiri, E. Reina, K. Genrich, S. Mehrotra, S. Setty, B. Smith, and A. Bartholomew. 2008. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur. J. Immunol. 38: 1745-1755. https://doi.org/10.1002/eji.200738129
  34. Yanez, R., M. L. Lamana, J. Garcia-Castro, I. Colmenero, M. Ramirez, and J. A. Bueren. 2006. Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem. Cells. 24: 2582-2591. https://doi.org/10.1634/stemcells.2006-0228
  35. Jang, M. J., H. S. Kim, H. G. Lee, G. J. Kim, H. G. Jeon, H. S. Shin, S. K. Chang, G. H. Hur, S. Y. Chong, D. Oh, and H. M. Chung. 2013. Placenta-derived mesenchymal stem cells have an immunomodulatory effect that can control acute graft-versus-host disease in mice. Acta. Haematol. 129: 197-206 https://doi.org/10.1159/000345267

Cited by

  1. Manufacture of Clinical-Grade Human Clonal Mesenchymal Stem Cell Products from Single Colony Forming Unit-Derived Colonies Based on the Subfractionation Culturing Method vol.21, pp.12, 2013, https://doi.org/10.1089/ten.tec.2015.0017
  2. Enhanced survival of human mesenchymal stem cells following co-delivery with glucagon-like peptide-1 analogue in fibrin gel vol.45, pp.2, 2013, https://doi.org/10.1007/s40005-014-0156-x
  3. Pharmacokinetics and In Vivo Fate of Intra-Articularly Transplanted Human Bone Marrow-Derived Clonal Mesenchymal Stem Cells vol.24, pp.9, 2015, https://doi.org/10.1089/scd.2014.0240
  4. Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway vol.4, pp.5, 2013, https://doi.org/10.5966/sctm.2014-0267
  5. Characterization of adipose tissue mesenchymal stromal cell subsets with distinct plastic adherence vol.13, pp.1, 2013, https://doi.org/10.1007/s13770-015-0027-1
  6. No significant effects of Poly(I:C) on human umbilical cord-derived mesenchymal stem cells in the treatment of B6.MRL-Faslpr mice vol.64, pp.2, 2013, https://doi.org/10.1016/j.retram.2016.03.002
  7. Mesenchymal stem cells provide prophylaxis against acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: A meta-analysis of animal models vol.7, pp.38, 2013, https://doi.org/10.18632/oncotarget.11238
  8. Autologous and Allogeneic Equine Mesenchymal Stem Cells Exhibit Equivalent Immunomodulatory Properties In Vitro vol.26, pp.7, 2013, https://doi.org/10.1089/scd.2016.0266
  9. MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process vol.10, pp.6, 2013, https://doi.org/10.3390/cells10061320
  10. Immunomodulation effect of mesenchymal stem cells in islet transplantation vol.142, pp.None, 2013, https://doi.org/10.1016/j.biopha.2021.112042