Immunoresponse to Allogeneic Synovial or Xenogenic Mesenchymal Stromal Cells in a Co-Culture Model

Abstract

The purpose of our investigations was to measure, in a co-culture condition, the immunoresponse to allogeneic or xenogenic cells, selected as potential sources for cell therapy of arthritis. We challenged human spleen-derived cells (hSpl) by three different mechanisms: 1) exposure to donor allogeneic or xenogeneic cellular antigens; 2) exposure to donor cells transduced with adenoviral antigens (Ad) and 3) lipopolysaccharide (LPS), a known inflammatory immunostimulant. The immunoresponse to allogeneic human synovial-derived mesenchymal stromal cells alone or transduced with adenoviral green fluorescent protein (hSD-MSC or hSD-MSC/GFP) or the immunoresponse to xenogeneic equine mesenchymal stromal cells (eqMSC) or equine dermal fibroblasts (eqDFb), characterized by the proportion of CD3+, CD4+, and CD8+ human splenocytes (hSpl), was measured on Day 0 and Day 6 of co-culture by flow cytometry. In culture with hSD-MSC, hSD-MSC/GFP, eqDFb, or eqMSC, the proportion of CD3+ and CD8+ hSpl increased with time in culture but not with exposure to cell alloor xeno-antigens. Both hSD-MSC and hSD-MSC/GFP increased in number during culture and were not affected in viability or proliferation by co-culture with allogeneic hSpl. In this in vitro, primary exposure study, hSpl demonstrated a natural selection and adaptation to a short-term cell culture environment, and that neither allogeneic nor xenogeneic cell antigens incited a greater cellular immunoactivation than co-cultured hSpl alone.

Share and Cite:

S. Jump, D. Smith, D. Flanigan and A. Bertone, "Immunoresponse to Allogeneic Synovial or Xenogenic Mesenchymal Stromal Cells in a Co-Culture Model," CellBio, Vol. 2 No. 1, 2012, pp. 1-9. doi: 10.4236/ojcb.2012.21001.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] R. E. Newman, D. Yoo, M. A. LeRoux and A. Danilkovitch-Miagkova, “Treatment of Inflammatory Diseases with Mesenchymal Stem Cells,” Inflammation & Allergy—Drug Targets, Vol. 8, No. 2, 2009, pp. 110-123. doi:10.2174/187152809788462635
[2] M. Brittberg, “Autologous Chondrocyte Transplantation,” Clinical Orthopaedics Related Research, Vol. 367, 1999, pp. 147-155. doi:10.1097/00003086-199910001-00016
[3] M. Brittberg, “Autologous Chondrocyte Implantation— Technique and Long-Term Follow-Up,” Injury, Vol. 39 No. 1, pp. 40-49. doi:10.1016/j.injury.2008.01.040
[4] P. D. Gikas, L. Bayliss, G. Bentley and T. W. Briggs, “An Overview of Autologous Chondrocyte Implantation,” The Journal of Bone & Joint Surgery (British Volume), Vol. 91, 2009, pp. 997-1006. doi:10.1302/0301-620X.91B8.21824
[5] J. D. Harris, R. A. Siston, X. Pan and D. C. Flanigan, “Autologous Chondrocyte Implantation: A Systematic Review,” The Journal of Bone & Joint Surgery, Vol. 92, No. 12, 2010, pp. 2220-2233. doi:10.2106/JBJS.J.00049
[6] D. G. Jones and L. Peterson, “Autologous Chondrocyte Implantation,” Instructional Course Lecturers, Vol. 56, 2007, pp. 429-445.
[7] H. Nakamura, M. Tanaka, K. Masuko-Hongo, et al., “Enhanced Production of MMP-1, MMP-3, MMP-13, and RANTES by Interaction of Chondrocytes with Autologous T Cells,” Rheumatology International, Vol. 26, No. 11, 2006, pp. 984-990. doi:10.1007/s00296-006-0116-5
[8] P. A. Revell, V. Mayston, P. Lalor and P. Mapp, “The Synovial Membrane in Osteoarthritis: A Histological Study Including the Characterisation of the Cellular Infiltrate Present in Inflammatory Osteoarthritis Using Monoclonal Antibodies, ”Annals of the Rheumatic Diseases, Vol. 47, No. 4, 1988, pp. 300-307. doi:10.1136/ard.47.4.300
[9] L. I. Sakkas, C. Scanzello, N. Johansom, et al., “T Cells and T-Cell Cytokine Transcripts in the Synovial Membrane in Patients with Osteoarthritis, ” Clinical Vaccine Immunology, Vol. 5, No. 4, 1998, pp. 430-437.
[10] M. Pei, F. He, B. M. Boyce and V. L. Kish, “Repair of Full-Thickness Femoral Condyle Cartilage Defects Using Allogeneic Synovial Cell-Engineered Tissue Constructs,” Osteoarthritis and Cartilage, Vol. 17, No. 6, 2009, pp. 714-722. doi:10.1016/j.joca.2008.11.017
[11] M. Pei, Z. Yan, M. Shoukry and B. M. Boyce, “Failure of Xenoimplantation Using Porcine Synovium-Derived Stem Cell-Based Cartilage Tissue Constructs for the Repair of Rabbit Osteochondral Defects,”Journal Orthopaedic Research, Vol. 28, No. 8, 2010, pp. 1064-1070.
[12] V. M. Corrigall, E. Solau-Gervais and G. S. Panayi, “Lack of CD80 Expression by Fibroblast-Like Synoviocytes Leading to Anergy in T Lymphocytes,” Arthritis & Rheumatism, Vol. 43, No. 7, 2000, pp. 1606-1615. doi:10.1002/1529-0131(200007)43:7<1606::AID-ANR26>3.0.CO;2-O
[13] F. Djouad, V. Fritz, F. Apparailly, et al., “Reversal of the Immunosuppressive Properties of Mesenchymal Stem Cells by Tumor Necrosis Factor Alpha in Collagen-Induced Arthritis,” Arthritis & Rheumatism, Vol. 52, No. 5, 2005, pp. 1595-1603. doi:10.1002/art.21012
[14] N. Nikolaeva, E. Uss, E. M. van Leeuwen, R. A. van Lier and I. J. ten Berge, “Differentiation of Human Alloreactive CD4+ and CD8+ T Cells in Vitro, ” Transplantation, Vol. 78, No. 6, 2004, pp. 815-824. doi:10.1097/01.TP.0000133308.60226.FA
[15] P. Renner, E. Eggenhofer, A. Rosenauer, et al., “Mesenchymal Stem Cells Require a Sufficient, Ongoing Immune Response to Exert Their Immunosuppressive Function,” Transplantation Proceeding, Vol. 41, No. 6, 2009, pp. 2607-2611. doi:10.1016/j.transproceed.2009.06.119
[16] P. Renner, F. C. Popp, E. Eggenhofer, et al., “Antigen-Specific Recognition Is Critical for the Function of Regulatory CD8+CD28– T Cells,” Transplant Immunology, Vol. 22, No. 3-4, 2010, pp. 144-149. doi:10.1016/j.trim.2009.10.002
[17] R. Maccario, M. Podestá, A. Moretta, et al., “Interaction of Human Mesenchymal Stem Cells with Cells Involved in Alloantigen-Specific Immune Response Favors the Differentiation of CD4+ T-Cell Subsets Expressing a Regulatory/Suppressive Phenotype,” Haematologica, Vol. 90, No. 4, 2005, pp. 516-525.
[18] L. A. Fortier, A. J. Nixon, J. Williams and C. S. Cable, “Isolation and Chondrocytic Differentiation of Equine Bone Marrow-Derived Mesenchymal Stem Cells,” American Journal of Veterinary Research, Vol. 59, No. 9, 1998, pp. 1182-1187.
[19] A. Ishihara, T. A. Zachos, J. S. Bartlett and A. L. Bertone, “Evaluation of Permissiveness and Cytotoxic Effects in Equine Chondrocytes, Synovial Cells, and Stem Cells in Response to Infection with Adenovirus 5 Vectors for Gene Delivery,” American Journal of Veterinary Research, Vol. 67, No. 7, 2006, pp. 1145-1155. doi:10.2460/ajvr.67.7.1145
[20] A. Ishihara, L. J. Zekas, A. S. Litsky, S. E. Weisbrode and A. L. Bertone, “Dermal Fibroblast-Mediated BMP2 Therapy to Accelerate Bone Healing in an Equine Osteotomy Model, ” Journal of Orthopaedic Research, Vol. 28, No. 3, 2010, pp. 403-411.
[21] T. A. Zachos, K. M. Shields and A. L. Bertone, “Gene-Mediated Osteogenic Differentiation of Stem Cells by Bone Morphogenetic Proteins-2 or -6, ” Journal of Orthopaedic Research, Vol. 24, No. 6, 2006, pp. 1279-1291. doi:10.1002/jor.20068
[22] A. Ishihara, L. J. Zekas, S. E. Weisbrode and A. L. Bertone, “Comparative Efficacy of Dermal Fibroblast-Mediated and Direct Adenoviral Bone Morphogenetic Protein-2 Gene Therapy for Bone Regeneration in an Equine Rib Model, ” Gene Therapy, Vol. 17, 2010, pp. 733-744. doi:10.1038/gt.2010.13
[23] C. H. Jo, H. J. Ahn, H. J. Kim, S. C. Seong and M. C. Lee, “Surface Characterization and Chondrogenic Differentiation of Mesenchymal Stromal Cells Derived from Synovium, ” Cytotherapy, Vol. 9, No. 4, 2007, pp. 316-327. doi:10.1080/14653240701291620
[24] K. B. Van Landuyt, E. A. Jones, D. McGonagle, F. P. Luyten and R. J. Lories, “Flow Cytometric Characterization of Freshly Isolated and Culture Expanded Human Synovial Cell Populations in Patients with Chronic Arthritis,” Arthritis Research & Therapy, Vol. 12, 2010, p. R15. doi:10.1186/ar2916
[25] P. N. Boyaka, A. Tafaro, R. Fischer, et al., “Effective Mucosal Immunity to Anthrax: Neutralizing Antibodies and Th Cell Responses Following Nasal Immunization with Protective Antigen,” Journal of Immunology, Vol. 170, No. 11, 2003, pp. 5636-5643.
[26] T. Fukuiwa, S. Sekine, R. Kobayashi, et al., “A Combination of Flt3 ligand cDNA and CpG ODN as Nasal Adjuvant Elicits NALT Dendritic Cells for Prolonged Mucosal Immunity,” Vaccine, Vol. 26, No. 37, 2008, pp. 4849-4859. doi:10.1016/j.vaccine.2008.06.091
[27] H. D. Adkisson, C. Milliman, X. Zhang, et al., “Immune Evasion by Neocartilage-Derived Chondrocytes: Implications for Biologic Repair of Joint Articular Cartilage,” Stem Cell Research, Vol. 4, No. 1, 2010, pp. 57-68. doi:10.1016/j.scr.2009.09.004
[28] C. J. Centeno, D. Busse, J. Kisiday, et al., “Regeneration of Meniscus Cartilage in a Knee Treated with Percutaneously Implanted Autologous Mesenchymal Stem Cells,” Medical Hypotheses, Vol. 71, No. 6, 2008, pp. 900-908. doi:10.1016/j.mehy.2008.06.042
[29] M. Horie, I. Sekiya, T. Muneta, et al., “Intra-Articular Injected Synovial Stem Cells Differentiate into Meniscal Cells Directly and Promote Meniscal Regeneration without Mobilization to Distant Organs in Rat Massive Meniscal Defect,” Stem Cells, Vol. 27, No. 4, 2009, pp. 878-887. doi:10.1634/stemcells.2008-0616
[30] Q. V. Jichen, G. Che, G. Jiang, et al., “Immune Suppression Produced by Intrathymic Inoculation with Xenogeneic Antigen and Whole-Body γ-Irradiation in a Pig-to-Monkey Heart Transplantation Model,” Transplantation Proceeding, Vol. 42, No. 9, 2010, pp. 3759-3762. doi:10.1016/j.transproceed.2010.06.040
[31] Y. Wang, X. Che, M. A. Armstrong and G. Li, “Survival of Bone Marrow-Derived Mesenchymal Stem Cells in a Xenotransplantation Model,” Journal Orthopaedic Research, Vol. 25, No. 7, 2007, pp. 926-932. doi:10.1002/jor.20385
[32] J. L. C. van Susante, P. Buma, L. Schuman, et al., “Resurfacing Potential of Heterologous Chondrocytes Suspended in Fibrin Glue in Large Full-Thickness Defects of Femoral Articular Cartilage: An Experimental Study in the Goat,” Biomaterials, Vol. 20, No. 13, 1999, pp. 1167-1175. doi:10.1016/S0142-9612(97)00190-7
[33] F. Djouad, C. Bony, T. H?upl, et al., “Transcriptional Profiles Discriminate Bone Marrow-Derived and Synovium-Derived Mesenchymal Stem Cells,” Arthritis Research & Therapy, Vol. 7, 2005, pp. R1304-R1315. doi:10.1186/ar1827

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.