Abstract
Adipose-derived mesenchymal stem or stromal cells (ASCs) are poised for clinical use in an allogeneic setting. Although ASCs have been shown to be nonimmunogenic by several laboratories, it is advisable for the investigator to confirm this for ASCs used in their studies due to variations in ASC production and the animal models in which they are used. We describe here the use of the mixed lymphocyte reaction (MLR) assay to determine immunogenicity and suppression by ASCs in vitro as well as assessing T cell responses to allogeneic ASC transplantation in vivo. A flow cytometry assay to determine serum antibody titer to transplanted ASCs is also described.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Di Nicola, M., Carlo-Stella, C., Magni, M., Milanesi, M., Longoni, P.D., Matteucci, P., Grisanti, S., and Gianni, A.M. (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99, 3838–43.
Le Blanc, K., Tammik, L., Sundberg, B., Haynesworth, S.E., and 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.
Tse, W.T., Pendleton, J.D., Bever, W.M., Egalka, M.C., and Guinan, E.C. (2003) Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 75, 389–97.
Klyushnenkova, E., Mosca, J.D., Zernetkina, V., Majumdar, M.K., Beggs, K.J., Simonetti, D.W., Deans, R.J., and McIntosh, K.R. (2005) T cell responses to allogeneic human mesenchymal stem cells: immunogenicity tolerance, and suppression. J Biomed Sci 12, 47–57.
Puissant, B., Barreau, C., Bourin, P., Clavel, C., Corre, J., Bousquet, C., Taureau, C., Cousin, B., Abbal, M., Laharrague, P., Penicaud, L., Casteilla, L., and Blancher, A. (2005) Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br J Haematol 129, 118–29.
McIntosh, K., Zvonic, S., Garrett, S., Mitchell, J.B., Floyd, Z.E., Hammill, L., Kloster, A., Di Halvorsen, Y., Ting, J.P., Storms, R.W., Goh, B., Kilroy, G., Wu, X., and Gimble, J.M. (2006) The immunogenicity of human adipose derived cells: temporal changes in vitro. Stem Cells 24, 1246–53.
Hoogduijn, M.J., Crop, M.J., Peeters, A.M.A., Van Osch, G.J.V.M., Balk, A.H.M.M., Ijzermans, J.N.M., Weimar, W., and Baan, C.C. (2007) Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells Dev 16, 597–604.
Niemeyer, P., Kornacker, M., Melhorn, A., Seckinger, A., Vohrer, J., Schmal, H., Kasten, P., Eckstein, V., Soudkamp, N.P., and Krause, U. (2007) Comparison of immunological properties of bone marrow stromal cells and adipose tissue-derived stem cells before and after osteogenic differentiation in vitro. Tissue Eng Part A 13, 111–21.
Wolbank, S., Peterbauer, A., Fahrner, M., Hennerbichler, S., van Griensven, M., Stadler, G., Redl, H., and Gabriel, C. (2007) Dose-dependent immunomodulatory effect of human stem cells from amniotic membrane: a comparison with human mesenchymal stem cells from adipose tissue. Tissue Eng Part A 13, 1173–83.
Cui, L., Yin, S., Liu, W., Li, N., Zhang, W., and Cao, Y. (2007) Expanded adipose-derived stem cells suppress mixed lymphocyte reaction by secretion of prostaglandin E2. Tissue Eng Part A 13, 1185–95.
Dai, W., Hale, S.L., Martin, B.J., Kuang, J.-Q., Dow, J.S., Wold, L.E., and Kloner, R.A. (2005) Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation 112, 214–23.
Gal, P., Necas, A., Planka, L., Kecova, H., Kren, L., Krupa, P., Hlucilova, J., Usvald, D. (2007) Chondrogenic potential of allogeneic mesenchymal stem cells transplanted without immunosuppression to regenerate physeal defect in rabbits. Acta Vet Brno 76, 265–75.
Devine, S.M., Cobbs, C., Jennings, M., Bartholomew, A., Hoffman, R. (2003) Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 101, 2999–3001.
Le Blanc, K., Frassoni, F., Ball, L., Locatelli, F., Roelofs, H., Lewis, I., Lanino, E., Sundberg, B., Bernardo, M.E., Remberger, M., Dini, G., Egeler, R.M., Bacigalupo, A., Fibbe, W., and Ringdén, O. (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371, 1579–86.
Li, Y., McIntosh, K., Chen, J., Zhang, C., Gao, Q., Borneman, J., Raginski, K., Mitchell, J., Shen, L., Zhang, J., Lu, D., and Chopp, M. (2006) Allogeneic bone marrow stromal cells promote glial-axonal remodeling without immunologic sensitization after stroke in rats. Exp Neurol 198, 313–25.
Beggs, K.J., Lyubimov, A., Borneman, J.N., Bartholomew, A., Moseley, A., Dodds, R., Archambault, M.P., Smith, A.K., and McIntosh, K.R. (2006) Immunologic consequences of multiple high-dose administration of allogeneic mesenchymal stem cells to baboons. Cell Transplant 15, 711–21.
McIntosh, K.R., Lopez, M.J., Borneman, J.N., Spencer, N.D., Anderson, P., and Gimble, J.M. (2009) Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model. Tissue Eng Part A 15, 2677–86.
Zappia, E., Casazza, S., Pedemonte, E., Benvenuto, F., Bonanni, I., Gerdoni, E., Giunti, D., Ceravolo, A., Cazzanti, F., Frassoni, F., Mancardi, G., and Uccelli, A. (2005) Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T cell anergy. Blood 106,1755–61.
Zhou, H.P., Yi, D.H., Yu, S.Q., Sun, G.C., Cui, Q., Zhu, H.L., Liu, J.C., Zhang, J.Z., and Wu, T.J. (2006) Administration of donor-derived mesenchymal stem cells can prolong the survival of rat cardiac allograft. Transplant Proc 38, 3046–51.
Itakura, S., Asari, S., Rawson, J., Ito, T., Todorov, I., Liu, C.-P., Sasaki, N., Kandeel, F., and Mullen, Y. (2007) Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat. Am J Transplant 7, 336–46.
Gerdoni, E., Gallo, B., Casazza, S., Musio, S., Bonanni, I., Pedemonte, E., Mantegazza, R., Frassoni, F., Mancardi, G., Pedotti, R., and Uccelli, A. (2007) Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Transplantation 83, 783–90.
Augello, A., Tasso, R., Negrini, S.M., Cancedda, R., and Pennesi, G. (2007) Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum 56, 1175–86.
Spees, J.L., Gregory, C.A., Singh, H., Tucker, H.A., Peister, A., Lynch, P.J., Hsu, S.C., Smith, J., and Prockop, D.J. (2004) Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene therapy. Mol Ther 9, 747–56.
Sundin, M., Ringdén, O., Sundberg, B., Nava, S., Götherstrom, C., and Le Blanc, K. (2007) No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica 92, 1208–15.
Poncelet, A.J., Vercruysse, J., Saliez, A., and Gianello, P. (2007) Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo. Transplantation 83, 783–90.
Wang, Y., Chen, X., Armstrong, M.A., and Li, G. (2007) Survival of bone marrow-derived mesenchymal stem cells in a xenotransplantation model. J Orthop Res 25, 926–32.
Nauta, A.J., Westerhuis, G., Kruisselbrink, A.W., Lurvink, E.G.A., Willemze, R., and Fibbe, W.E. (2006) Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloblative setting. Blood 108, 2114–20.
Eliopoulos, N., Stagg, J., Lejeune, L., Pommey, S., and Galipeau, J. (2005) Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood 106, 4057–65.
Tolar, J., O’Shaughnessy, M.J., Panoskaltsis-Mortari, A., McElmurry, R.T., Bell, S., Riddle, M., McIvor, R.S., Yant, S.R., Kay, M.A., Krause, D., Verfaille, C.M., and Blazar, B.R. (2006) Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells. Blood 107, 4182–8.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
McIntosh, K.R. (2011). Evaluation of Cellular and Humoral Immune Responses to Allogeneic Adipose-Derived Stem/Stromal Cells. In: Gimble, J., Bunnell, B. (eds) Adipose-Derived Stem Cells. Methods in Molecular Biology, vol 702. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61737-960-4_11
Download citation
DOI: https://doi.org/10.1007/978-1-61737-960-4_11
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-959-8
Online ISBN: 978-1-61737-960-4
eBook Packages: Springer Protocols