Event Abstract

Back to Event

An immunotherapy study to compare immunomodulatory effect of Human Mesenchymal Stromal Cells derived from Bone Marrow and Adipose tissues for application in non-human primate kidney transplantation

Fattah Sotoodehnejadnematalahi1*, Hossein Baharvand2 and Nasser Aghdami1
  • 1 Department of Regenerative Biomedicine at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  • 2 Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

Multipotent non-hematopoietic progenitor mesenchymal stem cells are originally isolated from bone marrow (BM) as well as adipose tissues and they are capable of differentiating into various mesodermal lineages. Several studies have reported low immunogenicity for MSCs as they appear to have great potential to be used as modulators of immune responses in a variety of diseases related to alloreactive immunity in addition to organ transplantation. In vitro studies have shown immunosuppressive effect of MSCs on T cells, B cells and natural killer cells as well as in vivo prolong skin graft survival. Studies have proposed human adipose tissues (hAD) as an unlimited source of MSCs which showed to have very similar immunological properties to MSCs derived from hBM. As MSCs isolation from BM knows as an aggressive method, therefore in this project we aim to isolate MSCs from adipose tissues and then study in vivo immunomodulatory effect of hAD-MSCs on immune responses in kidney xenograft. In addition, we aim to compare the immune regulation of hAD-MSCs in kidney transplantation in non-human primates with hBM-MSCs and identify any possible immunomodulative differences between hAD-MSCs and hBM-MSCs. The understanding of immune modulation consequences by hMSCs is required for their use as derivatives of adipose tissues which provide cells for immunotherapy in clinical applications

References

• AGGARWAL, S. & PITTENGER, M. F. (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 105, 1815-22.

• BAI, L., LENNON, D. P., EATON, V., MAIER, K., CAPLAN, A. I., MILLER, S. D. & MILLER, R. H. (2009) Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia, 57, 1192-203.

• BARBERI, T., WILLIS, L. M., SOCCI, N. D. & STUDER, L. (2005) Derivation of multipotent mesenchymal precursors from human embryonic stem cells. PLoS Med, 2, e161.

• BEYTH, S., BOROVSKY, Z., MEVORACH, D., LIEBERGALL, M., GAZIT, Z., ASLAN, H., GALUN, E. & RACHMILEWITZ, J. (2005) Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood, 105, 2214-9.

• BIEBACK, K., KERN, S., KLUTER, H. & EICHLER, H. (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells, 22, 625-34.

• CAMPAGNOLI, C., ROBERTS, I. A., KUMAR, S., BENNETT, P. R., BELLANTUONO, I. & FISK, N. M. (2001) Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood, 98, 2396-402.

• CORCIONE, A., BENVENUTO, F., FERRETTI, E., GIUNTI, D., CAPPIELLO, V., CAZZANTI, F., RISSO, M., GUALANDI, F., MANCARDI, G. L., PISTOIA, V. & UCCELLI, A. (2006) Human mesenchymal stem cells modulate B-cell functions. Blood, 107, 367-72.

• DA SILVA MEIRELLES, L., CHAGASTELLES, P. C. & NARDI, N. B. (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci, 119, 2204-13.

• DI NICOLA, M., CARLO-STELLA, C., MAGNI, M., MILANESI, M., LONGONI, P. D., MATTEUCCI, P., GRISANTI, S. & GIANNI, A. M. (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 99, 3838-43.

• DJOUAD, F., PLENCE, P., BONY, C., TROPEL, P., APPARAILLY, F., SANY, J., NOEL, D. & JORGENSEN, C. (2003) Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood, 102, 3837-44.

• DOMINICI, M., LE BLANC, K., MUELLER, I., SLAPER-CORTENBACH, I., MARINI, F., KRAUSE, D.,DEANS, R., KEATING, A., PROCKOP, D. & HORWITZ, E. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315-7.

• DOMINICI, M., PAOLUCCI, P., CONTE, P. & HORWITZ, E. M. (2009) Heterogeneity of multipotent mesenchymal stromal cells: from stromal cells to stem cells and vice versa. Transplantation, 87, S36-42.

• GRINNEMO, K. H., MANSSON, A., DELLGREN, G., KLINGBERG, D., WARDELL, E., DRVOTA, V., TAMMIK, C., HOLGERSSON, J., RINGDEN, O., SYLVEN, C. & LE BLANC, K. (2004) Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infarcted rat myocardium. J Thorac Cardiovasc Surg, 127, 1293-300.

• HORWITZ, E. M., LE BLANC, K., DOMINICI, M., MUELLER, I., SLAPER-CORTENBACH, I., MARINI, F. C., DEANS, R. J., KRAUSE, D. S. & KEATING, A. (2005) Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy, 7, 393-5.

• JIANG, X. X., ZHANG, Y., LIU, B., ZHANG, S. X., WU, Y., YU, X. D. & MAO, N. (2005) Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood, 105, 4120-6.

• KLYUSHNENKOVA, E., MOSCA, J. D., ZERNETKINA, V., MAJUMDAR, M. K., BEGGS, K. J., SIMONETTI, D. W., DEANS, R. J. & MCINTOSH, K. R. (2005) T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci, 12, 47-57.

• LE BLANC, K., TAMMIK, L., SUNDBERG, B., HAYNESWORTH, S. E. & RINGDEN, O. (2003) Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol, 57, 11-20.

• LURIA, E. A., PANASYUK, A. F. & FRIEDENSTEIN, A. Y. (1971) Fibroblast colony formation from monolayer cultures of blood cells. Transfusion, 11, 345-9.

• NASEF, A., MAZURIER, C., BOUCHET, S., FRANCOIS, S., CHAPEL, A., THIERRY, D., GORIN, N. C. & FOUILLARD, L. (2008) Leukemia inhibitory factor: Role in human mesenchymal stem cells mediated immunosuppression. Cell Immunol, 253, 16-22.

• NAUTA, A. J., KRUISSELBRINK, A. B., LURVINK, E., WILLEMZE, R. & FIBBE, W. E. (2006) Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J Immunol, 177, 2080-7.

• NEMETH, K., LEELAHAVANICHKUL, A., YUEN, P. S., MAYER, B., PARMELEE, A., DOI, K., ROBEY, P. G., LEELAHAVANICHKUL, K., KOLLER, B. H., BROWN, J. M., HU, X., JELINEK, I., STAR, R. A. & MEZEY, E. (2009) Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med, 15, 42-9.

• NIEMEYER, P., VOHRER, J., SCHMAL, H., KASTEN, P., FELLENBERG, J., SUEDKAMP, N. P. & MEHLHORN, A. T. (2008) Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice. Cytotherapy, 10, 784-95.

• PITTENGER, M. F., MACKAY, A. M., BECK, S. C., JAISWAL, R. K., DOUGLAS, R., MOSCA, J. D., MOORMAN, M. A., SIMONETTI, D. W., CRAIG, S. & MARSHAK, D. R. (1999) Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143-7.

• PREVOSTO, C., ZANCOLLI, M., CANEVALI, P., ZOCCHI, M. R. & POGGI, A. (2007) Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction. Haematologica, 92, 881-8.

• PROCKOP, D. J. (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science, 276, 71-4.

• RAFFAGHELLO, L., BIANCHI, G., BERTOLOTTO, M., MONTECUCCO, F., BUSCA, A., DALLEGRI, F., OTTONELLO, L. & PISTOIA, V. (2008) Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem Cells, 26, 151-62.

• RASMUSSON, I., RINGDEN, O., SUNDBERG, B. & LE BLANC, K. (2003) Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation, 76, 1208-13.

• SATO, K., OZAKI, K., OH, I., MEGURO, A., HATANAKA, K., NAGAI, T., MUROI, K. & OZAWA, K. (2007) Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood, 109, 228-34.

• SEMEDO, P., CORREA-COSTA, M., ANTONIO CENEDEZE, M., MARIA AVANCINI COSTA MALHEIROS, D., ANTONIA DOS REIS, M., SHIMIZU, M. H., SEGURO, A. C., PACHECO-SILVA, A. & SARAIVA CAMARA, N. O. (2009) Mesenchymal stem cells attenuate renal fibrosis through immune modulation and remodeling properties in a rat remnant kidney model. Stem Cells, 27, 3063-73.

• SOTIROPOULOU, P. A., PEREZ, S. A., GRITZAPIS, A. D., BAXEVANIS, C. N. & PAPAMICHAIL, M. (2006) Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells, 24, 74-85.

• SPAGGIARI, G. M., CAPOBIANCO, A., ABDELRAZIK, H., BECCHETTI, F., MINGARI, M. C. & MORETTA, L. (2008) Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood, 111, 1327-33.

• TAN, Z., SU, Z. Y., WU, R. R., GU, B., LIU, Y. K., ZHAO, X. L. & ZHANG, M. Immunomodulative effects of mesenchymal stem cells derived from human embryonic stem cells in vivo and in vitro. J Zhejiang Univ Sci B, 12, 18-27.

• TRIVEDI, P. & HEMATTI, P. (2008) Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells. Exp Hematol, 36, 350-9.

• WILLIAMS, J. T., SOUTHERLAND, S. S., SOUZA, J., CALCUTT, A. F. & CARTLEDGE, R. G. (1999) Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. Am Surg, 65, 22-6.

• XU, C., JIANG, J., SOTTILE, V., MCWHIR, J., LEBKOWSKI, J. & CARPENTER, M. K. (2004) Immortalized fibroblast-like cells derived from human embryonic stem cells support undifferentiated cell growth. Stem Cells, 22, 972-80.

• ZHANG, W., GE, W., LI, C., YOU, S., LIAO, L., HAN, Q., DENG, W. & ZHAO, R. C. (2004) Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev, 13, 263-71.

• ZUK, P. A., ZHU, M., MIZUNO, H., HUANG, J., FUTRELL, J. W., KATZ, A. J., BENHAIM, P., LORENZ, H. P. & HEDRICK, M. H. (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng, 7, 211-28

Keywords: Mesenchymal Stem Cells, Adipose tissues, immunosuppressive, immunomodulatory, Kidney Transplantation

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Translational immunology and immune intervention

Citation: Sotoodehnejadnematalahi F, Baharvand H and Aghdami N (2013). An immunotherapy study to compare immunomodulatory effect of Human Mesenchymal Stromal Cells derived from Bone Marrow and Adipose tissues for application in non-human primate kidney transplantation. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00003

Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.

The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.

Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.

For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.

Received: 09 Mar 2013; Published Online: 22 Aug 2013.

* Correspondence: Dr. Fattah Sotoodehnejadnematalahi, Department of Regenerative Biomedicine at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Tehran, Iran, fattah212@gmail.com