Background: Mesenchymal stromal cells (MSC) are being tested for the treatment of immune diseases. MSC are present in several adult tissues which milieu may influence MSC behavior particularly under inflammatory conditions. Additionally, culture conditions also can modify cell function or state of activation. Methods: To address the influence of the MSC source on its characteristics, we studied a xenofree, platelet lysate supplemented MSC from dental pulp, adipose tissue and bone marrow, co-cultured with isolated T cells and PBMC subset, and studied the effect of culture animal or human supplements immunomodulatory effect. Results: All three sources were efficient in inhibiting T cells. Among all MSC sources, as also described by others, adipose MSC was capable to significantly induce Treg phenotype and decrease T CD8+. Furthermore, comparing fetal bovine serum and platelet lysate, results demonstrate that platelet lysate alone is capable to induce immunomodulatory phenotype. Additional studies have to be made to elucidate the PL immunomodulatory effect.
References
[1]
Friedenstein, A.J., Chailakhyan, R.K. and Gerasimov, U.V. (1987) Bone Marrow Osteogenic Stem Cells: In Vitro Cultivation and Transplantation in Diffusion Chambers. Cell and Tissue Kinetics, 20, 263-272.
http://dx.doi.org/10.1111/j.1365-2184.1987.tb01309.x
[2]
Friedenstein, A.J., Gorskaja, J.F. and Kulagina, N.N. (1976) Fibroblast Precursors in Normal and Irradiated Mouse Hematopoietic Organs. Experimental Hematology, 4, 267-274.
[3]
Wang, Y., Chen, X., Cao, W. and Shi, Y. (2014) Plasticity of Mesenchymal Stem Cells in Immunomodulation: Pathological and Therapeutic Implications. Nature Immunology, 15, 1009-1016. http://dx.doi.org/10.1038/ni.3002
[4]
Laranjeira, P., Pedrosa, M., Pedreiro, S., Gomes, J., Martinho, A., Antunes, B., Ribeiro, T., Santos, F., Trindade, H. and Paiva, A. (2015) Effect of Human Bone Marrow Mesenchymal Stromal Cells on Cytokine Production by Peripheral Blood Naïve. Memory and Effector T Cells, 6, 1-14.
[5]
Yu, B., Zhang, X. and Li, X. (2014) Exosomes Derived from Mesenchymal Stem Cells. International Journal of Molecular Sciences, 15, 4142-4157. http://dx.doi.org/10.3390/ijms15034142
[6]
Via, A.G., Frizziero, A. and Oliva, F. (2012) Biological Properties of Mesenchymal Stem Cells from Different Sources. Muscle, Ligaments and Tendons Journal, 2, 154-162.
[7]
Sousa, B.R., Parreira, R.C., Fonseca, E.A., Amaya, M.J., Tonelli, F.M.P., Lacerda, S.M.S.N., Lalwani, P., Santos, A.K., Gomes, K.N., Ulrich, H., Kihara, A.H. and Resende, R.R. (2014) Human Adult Stem Cells from Diverse Origins: An Overview from Multiparametric Immunophenotyping to Clinical Applications. Cytometry Part A, 85, 43-77.
http://dx.doi.org/10.1002/cyto.a.22402
[8]
Jin, H., Bae, Y., Kim, M., Kwon, S.-J., Jeon, H., Choi, S., Kim, S., Yang, Y., Oh, W. and Chang, J. (2013) Comparative Analysis of Human Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue, and Umbilical Cord Blood as Sources of Cell Therapy. International Journal of Molecular Sciences, 14, 17986-18001.
http://dx.doi.org/10.3390/ijms140917986
[9]
Silla, L., Valim, V., Amorin, B., Alegretti, A.P., Dos Santos de Oliveira, F., Lima da Silva, M.A., Dahmer, A., Emerim Lemos, N., Mentz Albrecht, M.A., Macedo Laureano, á., Bonfim, C., Moraes Júnior, L., Pezzi, A., Baggio, L., Albrecht, C.A.M., Capra, M., Fogliatto, L., Della Costa Rigoni, L., Fischer, G., Paz, A. and Esteves Daudt, L. (2014) A Safety and Feasibility Study with Platelet Lysate Expanded Bone Marrow Mesenchymal Stromal Cells for the Treatment of Acute Graft-versus-Host Disease in Brazil. Leukemia & Lymphoma, 55, 1203-1205.
http://dx.doi.org/10.3109/10428194.2013.823495
[10]
Iudicone, P., Fioravanti, D., Bonanno, G., Miceli, M., Lavorino, C., Totta, P., Frati, L., Nuti, M. and Pierelli, L. (2014) Pathogen-Free, Plasma-Poor Platelet Lysate and Expansion of Human Mesenchymal Stem Cells. Journal of Translational Medicine, 12, 28. http://dx.doi.org/10.1186/1479-5876-12-28
[11]
Horwitz, E.M., Le Blanc, K., Dominici, M., Mueller, I., Slaper-Cortenbach, I., Marini, F.C., Deans, R.J., Krause, D.S. and Keating, A. (2005) Clarification of the Nomenclature for MSC: The International Society for Cellular Therapy Position Statement. Cytotherapy, 7, 393-395. http://dx.doi.org/10.1080/14653240500319234
[12]
Haddad, R. and Saldanha-Araujo, F. (2014) Mechanisms of T-Cell Immunosuppression by Mesenchymal Stromal Cells: What Do We Know so Far? BioMed Research International, 2014, 1-14. http://dx.doi.org/10.1155/2014/216806
[13]
Zuk, P.A., Zhu, M., Mizuno, H., Huang, J., Futrell, J.W., Katz, A.J., Benhaim, P., Lorenz, H.P. and Hedrick, M.H. Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies. Tissue Engineering, 7, 211-228. http://dx.doi.org/10.1089/107632701300062859
[14]
Capelli, C., Domenghini, M., Borleri, G., Bellavita, P., Poma, R., Carobbio, A., Micò, C., Rambaldi, A., Golay, J. and Introna, M. (2007) Human Platelet Lysate Allows Expansion and Clinical Grade Production of Mesenchymal Stromal Cells from Small Samples of Bone Marrow Aspirates or Marrow Filter Washouts. Bone Marrow Transplant, 40, 785-791. http://dx.doi.org/10.1038/sj.bmt.1705798
[15]
Gronthos, S., Mankani, M., Brahim, J., Robey, P.G. and Shi, S. (2000) Postnatal Human Dental Pulp Stem Cells (DPSCs) in Vitro and in Vivo. Proceedings of the National Academy of Sciences of the United States of America, 97, 13625-13630. http://dx.doi.org/10.1073/pnas.240309797
[16]
Rasmusson, I., Ringdén, O., Sundberg, B. and Le Blanc, K. (2005) Mesenchymal Stem Cells Inhibit Lymphocyte Proliferation by Mitogens and Alloantigens by Different Mechanisms. Experimental Cell Research, 305, 33-41.
http://dx.doi.org/10.1016/j.yexcr.2004.12.013
[17]
Le Blanc, K., Rasmusson, I., Sundberg, B., Götherström, C., Hassan, M., Uzunel, M. and Ringdén, O. (2004) Treatment of Severe Acute Graft-versus-Host Disease with Third Party Haploidentical Mesenchymal Stem Cells. The Lancet, 363, 1439-1441. http://dx.doi.org/10.1016/S0140-6736(04)16104-7
[18]
Caplan, A.I. and Correa, D. (2011) The MSC: An Injury Drugstore. Cell Stem Cell, 9, 11-15.
http://dx.doi.org/10.1016/j.stem.2011.06.008
[19]
Hemeda, H., Giebel, B. and Wagner, W. (2014) Evaluation of Human Platelet Lysate versus Fetal Bovine Serum for Culture of Mesenchymal Stromal Cells. Cytotherapy, 16, 170-180.
http://dx.doi.org/10.1016/j.jcyt.2013.11.004
[20]
Mohammadzadeh, A., Pourfathollah, A.A., Shahrokhi, S., Hashemi, S.M., Moradi, S.L.A. and Soleimani, M. (2014) Immunomodulatory Effects of Adipose-Derived Mesenchymal Stem Cells on the Gene Expression of Major Transcription Factors of T Cell Subsets. International Immunopharmacology, 20, 316-321.
http://dx.doi.org/10.1016/j.intimp.2014.03.003
[21]
Socié, G. and Blazar, B.R. (2009) Acute Graft-versus-Host Disease: From the Bench to the Bedside. Blood, 114, 4327-4736. http://dx.doi.org/10.1182/blood-2009-06-204669
[22]
Wing, K. and Sakaguchi, S. (2010) Regulatory T Cells Exert Checks and Balances on Self Tolerance and Autoimmunity. Nature Immunology, 11, 7-13. http://dx.doi.org/10.1038/ni.1818
[23]
Durutürk, L., Sarü, S. and Sengül, A. (2013) Immunocompetent Cell Level as a Diagnostic Reference for Pulpal Pathosis of Primary Teeth. Archives of Oral Biology, 58, 1517-1522.
http://dx.doi.org/10.1016/j.archoralbio.2013.04.010
[24]
Hahn, C.L., Best, A.M. and Tew, J.G. (2000) Cytokine Induction by Streptococcus mutans and Pulpal Pathogenesis. Infection and Immunity, 68, 6785-6789. http://dx.doi.org/10.1128/IAI.68.12.6785-6789.2000
[25]
Lee, Y.-L., Lee, L.-W., Su, C.-Y., Hsiao, G., Yang, Y.-Y., Leu, S.-J., Shieh, Y.-H. and Burnouf, T. (2013) Virally Inactivated Human Platelet Concentrate Lysate Induces Regulatory T Cells and Immunosuppressive Effect in a Murine Asthma Model. Transfusion, 53, 1918-1928. http://dx.doi.org/10.1111/trf.12068
[26]
Paczesny, S., Raiker, N., Brooks, S. and Mumaw, C. (2013) Graft-versus-Host Disease Biomarkers: Omics and Personalized Medicine. International Journal of Hematology, 98, 275-292. http://dx.doi.org/10.1007/s12185-013-1406-9
[27]
Visentainer, J.E.L., Lieber, S.R., Persoli, L.B.L., Vigorito, A.C., Aranha, F.J.P., de Brito Eid, K.A., Oliveira, G.B., Miranda, E.C.M. and de Souza, C.A. (2003) Serum Cytokine Levels and Acute Graft-versus-Host Disease after HLA-Identical Hematopoietic Stem Cell Transplantation. Experimental Hematology, 31, 1044-1050.
http://dx.doi.org/10.1016/S0301-472X(03)00264-9
[28]
Fekete, N., Gadelorge, M., Fürst, D., Maurer, C., Dausend, J., Fleury-Cappellesso, S., Mailünder, V., Lotfi, R., Ignatius, A., Sensebé, L., Bourin, P., Schrezenmeier, H. and Rojewski, M.T. (2012) Platelet Lysate from Whole Blood-Derived Pooled Platelet Concentrates and Apheresis-Derived Platelet Concentrates for the Isolation and Expansion of Human Bone Marrow Mesenchymal Stromal Cells: Production Process, Content and Identification of Active Comp. Cytotherapy, 14, 540-554. http://dx.doi.org/10.3109/14653249.2012.655420
[29]
Horwitz, D.A., Zheng, S.G., Wang, J. and Gray, J.D. (2008) Critical Role of IL-2 and TGF-Beta in Generation, Function and Stabilization of Foxp3+CD4+ Treg. European Journal of Immunology, 38, 912-915.
http://dx.doi.org/10.1002/eji.200738109
