Journal of Veterinary Science

  • 제22권5호
  • /
  • Pages.63.1-63.14
  • /
  • 2021
  • /
  • 1229-845X(pISSN)
  • /
  • 1976-555X(eISSN)
대한수의학회 (The Korean Society of Veterinary Science)
권호 표지
DOI QR코드

DOI QR Code

Immunosuppression-enhancing effect of the administration of allogeneic canine adipose-derived mesenchymal stem cells (cA-MSCs) compared with autologous cA-MSCs in vitro

  • Wi, Hayeon (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration) ;
  • Lee, Seunghoon (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration) ;
  • Kim, Youngim (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration) ;
  • No, Jin-Gu (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration) ;
  • Lee, Poongyeon (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration) ;
  • Lee, Bo Ram (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration) ;
  • Oh, Keon Bong (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration) ;
  • Hur, Tai-young (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration) ;
  • Ock, Sun A (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration)
  • 투고 : 2021.03.16
  • 심사 : 2021.07.04
  • 발행 : 2021.09.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: Recently, mesenchymal stem cells therapy has been performed in dogs, although the outcome is not always favorable. Objectives: To investigate the therapeutic efficacy of mesenchymal stem cells (MSCs) using dog leukocyte antigen (DLA) matching between the donor and recipient in vitro. Methods: Canine adipose-derived MSCs (cA-MSCs) isolated from the subcutaneous tissue of Dog 1 underwent characterization. For major DLA genotyping (DQA1, DQB1, and DRB1), peripheral blood mononuclear cells (PBMCs) from two dogs (Dogs 1 and 2) were analyzed by direct sequencing of polymerase chain reaction (PCR) products. The cA-MSCs were co-cultured at a 1:10 ratio with activated PBMCs (DLA matching or mismatching) for 3 days and analyzed for immunosuppressive (IDO, PTGS2, and PTGES), inflammatory (IL6 and IL10), and apoptotic genes (CASP8, BAX, TP53, and BCL2) by quantitative real-time reverse transcriptase-PCR. Results: cA-MSCs were expressed cell surface markers such as CD90+/44+/29+/45- and differentiated into osteocytes, chondrocytes, and adipocytes in vitro. According to the Immuno Polymorphism Database, DLA genotyping comparisons of Dogs 1 and 2 revealed complete differences in genes DQA1, DQB1, and DRB1. In the co-culturing of cA-MSCs and PBMCs, DLA mismatch between the two cell types induced a significant increase in the expression of immunosuppressive (IDO/PTGS2) and apoptotic (CASP8/BAX) genes. Conclusions: The administration of cA-MSCs matching the recipient DLA type can alleviate the need to regulate excessive immunosuppressive responses associated with genes, such as IDO and PTGES. Furthermore, easy and reliable DLA genotyping technology is required because of the high degree of genetic polymorphisms of DQA1, DQB1, and DRB1 and the low readability of DLA 88.

키워드

과제정보

This work was supported by the Cooperative Research Program of the Center for Companion Animal Research (Grant number PJ01395702) of the National Institute of Animal Science, Rural Development Administration, Republic of Korea.

참고문헌

  1. Dias IE, Pinto PO, Barros LC, Viegas CA, Dias IR, Carvalho PP. Mesenchymal stem cells therapy in companion animals: useful for immune-mediated diseases? BMC Vet Res. 2019;15(1):358. https://doi.org/10.1186/s12917-019-2087-2
  2. Ogliari KS, Marinowic D, Brum DE, Loth F. Stem cells in dermatology. An Bras Dermatol. 2014;89(2):286-291. https://doi.org/10.1590/abd1806-4841.20142530
  3. Iohara K, Utsunomiya S, Kohara S, Nakashima M. Allogeneic transplantation of mobilized dental pulp stem cells with the mismatched dog leukocyte antigen type is safe and efficacious for total pulp regeneration. Stem Cell Res Ther. 2018;9(1):116. https://doi.org/10.1186/s13287-018-0855-8
  4. Kot M, Baj-Krzyworzeka M, Szatanek R, Musial-Wysocka A, Suda-Szczurek M, Majka M. The importance of HLA assessment in "off-the-shelf " allogeneic mesenchymal stem cells based-therapies. Int J Mol Sci. 2019;20(22):5680. https://doi.org/10.3390/ijms20225680
  5. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143-147. https://doi.org/10.1126/science.284.5411.143
  6. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99(10):3838-3843. https://doi.org/10.1182/blood.V99.10.3838
  7. Drukker M, Katz G, Urbach A, Schuldiner M, Markel G, Itskovitz-Eldor J, et al. Characterization of the expression of MHC proteins in human embryonic stem cells. Proc Natl Acad Sci U S A. 2002;99(15):9864-9869. https://doi.org/10.1073/pnas.142298299
  8. Bocelli-Tyndall C, Zajac P, Di Maggio N, Trella E, Benvenuto F, Iezzi G, et al. Fibroblast growth factor 2 and platelet-derived growth factor, but not platelet lysate, induce proliferation-dependent, functional class II major histocompatibility complex antigen in human mesenchymal stem cells. Arthritis Rheum. 2010;62(12):3815-3825. https://doi.org/10.1002/art.27736
  9. Wang RF. The role of MHC class II-restricted tumor antigens and CD4+ T cells in antitumor immunity. Trends Immunol. 2001;22(5):269-276. https://doi.org/10.1016/S1471-4906(01)01896-8
  10. Wilbe M, Jokinen P, Hermanrud C, Kennedy LJ, Strandberg E, Hansson-Hamlin H, et al. MHC class II polymorphism is associated with a canine SLE-related disease complex. Immunogenetics. 2009;61(8):557-564. https://doi.org/10.1007/s00251-009-0387-6
  11. Poncelet AJ, Vercruysse J, Saliez A, Gianello P. Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo. Transplantation. 2007;83(6):783-790. https://doi.org/10.1097/01.tp.0000258649.23081.a3
  12. Cuervo B, Rubio M, Sopena J, Dominguez JM, Vilar J, Morales M, et al. Hip osteoarthritis in dogs: a randomized study using mesenchymal stem cells from adipose tissue and plasma rich in growth factors. Int J Mol Sci. 2014;15(8):13437-13460. https://doi.org/10.3390/ijms150813437
  13. Harman R, Carlson K, Gaynor J, Gustafson S, Dhupa S, Clement K, et al. A prospective, randomized, masked, and placebo-controlled efficacy study of intraarticular allogeneic adipose stem cells for the treatment of osteoarthritis in dogs. Front Vet Sci. 2016;3:81.
  14. Kol A, Wood JA, Carrade Holt DD, Gillette JA, Bohannon-Worsley LK, Puchalski SM, et al. Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses. Stem Cell Res Ther. 2015;6(1):73. https://doi.org/10.1186/s13287-015-0050-0
  15. Bunnell BA, Flaat M, Gagliardi C, Patel B, Ripoll C. Adipose-derived stem cells: isolation, expansion and differentiation. Methods. 2008;45(2):115-120. https://doi.org/10.1016/j.ymeth.2008.03.006
  16. Maredziak M, Smieszek A, Chrzastek K, Basinska K, Marycz K. Physical activity increases the total number of bone-marrow-derived mesenchymal stem cells, enhances their osteogenic potential, and inhibits their adipogenic properties. Stem Cells Int. 2015;2015:379093. https://doi.org/10.1155/2015/379093
  17. Barry F, Boynton RE, Liu B, Murphy JM. Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components. Exp Cell Res. 2001;268(2):189-200. https://doi.org/10.1006/excr.2001.5278
  18. Murgia C, Pritchard JK, Kim SY, Fassati A, Weiss RA. Clonal origin and evolution of a transmissible cancer. Cell. 2006;126(3):477-487. https://doi.org/10.1016/j.cell.2006.05.051
  19. Kennedy LJ, Barnes A, Short A, Brown JJ, Lester S, Seddon J, et al. Canine DLA diversity: 1. New alleles and haplotypes. Tissue Antigens. 2007;69 Suppl 1:272-288. https://doi.org/10.1111/j.1399-0039.2006.00779.x
  20. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt Method. Methods. 2001;25(4):402-408. https://doi.org/10.1006/meth.2001.1262
  21. Lee M, Jeong SY, Ha J, Kim M, Jin HJ, Kwon SJ, et al. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo. Biochem Biophys Res Commun. 2014;446(4):983-989. https://doi.org/10.1016/j.bbrc.2014.03.051
  22. Ock SA, Maeng GH, Lee YM, Kim TH, Kumar BM, Lee SL, et al. Donor-matched functional and molecular characterization of canine mesenchymal stem cells derived from different origins. Cell Transplant. 2013;22(12):2311-2321. https://doi.org/10.3727/096368912X657981
  23. Bertolo A, Steffen F, Malonzo-Marty C, Stoyanov J. Canine mesenchymal stem cell potential and the importance of dog breed: implication for cell-based therapies. Cell Transplant. 2015;24(10):1969-1980. https://doi.org/10.3727/096368914X685294
  24. Russell KA, Chow NH, Dukoff D, Gibson TW, LaMarre J, Betts DH, et al. Characterization and immunomodulatory effects of canine adipose tissue- and bone marrow-derived mesenchymal stromal cells. PLoS One. 2016;11(12):e0167442. https://doi.org/10.1371/journal.pone.0167442
  25. Hardt C, Ferencik S, Tak R, Hoogerbrugge PM, Wagner V, Grosse-Wilde H. Sequence-based typing reveals a novel DLA-88 allele, DLA-88*04501, in a beagle family. Tissue Antigens. 2006;67(2):163-165. https://doi.org/10.1111/j.1399-0039.2006.00497.x
  26. Tsai KL, Starr-Moss AN, Venkataraman GM, Robinson C, Kennedy LJ, Steiner JM, et al. Alleles of the major histocompatibility complex play a role in the pathogenesis of pancreatic acinar atrophy in dogs. Immunogenetics. 2013;65(7):501-509. https://doi.org/10.1007/s00251-013-0704-y
  27. Venkataraman GM, Kennedy LJ, Little ME, Graves SS, Harkey MA, Torok-Storb BJ, et al. Thirteen novel canine dog leukocyte antigen-88 alleles identified by sequence-based typing. HLA. 2017;90(3):165-170. https://doi.org/10.1111/tan.13077
  28. Miyamae J, Suzuki S, Katakura F, Uno S, Tanaka M, Okano M, et al. Identification of novel polymorphisms and two distinct haplotype structures in dog leukocyte antigen class I genes: DLA-88, DLA-12 and DLA-64. Immunogenetics. 2018;70(4):237-255. https://doi.org/10.1007/s00251-017-1031-5
  29. Chabannes D, Hill M, Merieau E, Rossignol J, Brion R, Soulillou JP, et al. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood. 2007;110(10):3691-3694. https://doi.org/10.1182/blood-2007-02-075481
  30. Yagi H, Soto-Gutierrez A, Parekkadan B, Kitagawa Y, Tompkins RG, Kobayashi N, et al. Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant. 2010;19(6):667-679. https://doi.org/10.3727/096368910X508762
  31. Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. 2016;7(1):e2062. https://doi.org/10.1038/cddis.2015.327
  32. de Windt TS, Saris DB, Slaper-Cortenbach IC, van Rijen MH, Gawlitta D, Creemers LB, et al. Direct cellcell contact with chondrocytes is a key mechanism in multipotent mesenchymal stromal cell-mediated chondrogenesis. Tissue Eng Part A. 2015;21(19-20):2536-2547. https://doi.org/10.1089/ten.tea.2014.0673
  33. Atsuta I, Liu S, Miura Y, Akiyama K, Chen C, An Y, et al. Mesenchymal stem cells inhibit multiple myeloma cells via the Fas/Fas ligand pathway. Stem Cell Res Ther. 2013;4(5):111. https://doi.org/10.1186/scrt322
  34. Kim JH, Lee YT, Hong JM, Hwang YI. Suppression of in vitro murine T cell proliferation by human adipose tissue-derived mesenchymal stem cells is dependent mainly on cyclooxygenase-2 expression. Anat Cell Biol. 2013;46(4):262-271. https://doi.org/10.5115/acb.2013.46.4.262
  35. Liu H, Shen Z, Wang Z, Wang X, Zhang H, Qin J, et al. Increased expression of IDO associates with poor postoperative clinical outcome of patients with gastric adenocarcinoma. Sci Rep. 2016;6(1):21319. https://doi.org/10.1038/srep21319