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COMPARISON OF THE IMMUNOMODULATORY PROPERTIES OF THE CORD BLOOD AND WHARTON’S JELLY DERIVED MESENCHYMAL STEM CELLS

Year 2023, Volume: 6 Issue: 2, 136 - 142, 26.06.2023
https://doi.org/10.26650/JARHS2023-1216719

Abstract

Objective: Mesenchymal stem cells (MSCs) are promising as a treatment option for many immune-related diseases due to their immune regulatory properties. Wharton’s Jelly (WJ-MSC) and cord blood (CB-MSC) have recently received more attention than the other MSC sources. In this study, it was aimed to investigate the difference in the mechanisms of the immunological effects of WJ-MSCs and CB-MSCs.
Material and Methods: The intracellular cytokine levels of peripheral blood mononuclear cells (PBMC) and CD4+ T cells before and after MSC co-culture (Interleukin-4 (IL-4), Interferon-γ (IFN-γ), and Interleukin-17 (IL17)) were determined by flow cytometry. At the same time, tumor growth factor (TGF)-β, IL-4, IL-17, IFN-γ supernatant cytokine levels were measured by ELISA. In the study, incubation times of 24 hours and 72 hours were applied with co-culture MSC/PBMC ratios of 1/5 and 1/10.
Results: Our data showed that WJ-MSCs and CB-MSCs have different morphological features, proliferation capacities, proliferation times and immunomodulating abilities. One of the cytokines of IFN-γ decreased significantly at both 1/5 and 1/10 ratios in the cell at 24 hours and increased significantly at 72 hours after CB-MSC/PBMC co-culture compared to the level after WJ-MSC/PBMC co-culture (p<0.05). Unlike for IL-17 cytokine, the intracellular level decreased significantly in the CB-MSC group only at 72 hours compared to the WJ-MSC group. For IL-4, the 1/10 ratio in the CB-MSC group decreased significantly at 24 hours, while the intracellular level was increased in all other groups. After CB-MSC/PBMC co-culture, TGF-β supernatant level decreased by 1/5 in 24 hours and increased in 72 hours. On the contrary, TGF-β supernatant level increased in the CB-MSC group at 24 hours and decreased significantly at 72 hours in 1/10 ratios (p<0.05).
Conclusion: CB-MSCs and WJ-MSCs show different immunomodulatory properties. Based on these findings, it can be said that the use of WJ-MSCs is more advantageous in terms of cell therapies due to the different isolation, proliferation capacity and immunomodulatory properties of CB-MSCs.

References

  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006;8(4):315-7. google scholar
  • Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004;363(9419):1439-41. google scholar
  • Atala A. Recent developments in tissue engineering and regenerative medicine. Curr Opin Pediatr 2006;18(2):167-71. google scholar
  • Stenderup K, Justesen J, Clausen C, Kassem M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 2003;33(6):919-26. google scholar
  • Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006;24(5):1294-301. google scholar
  • Zheng YB, Gao ZL, Xie C, Zhu HP, Peng L, Chen JH, et al. Characterization and hepatogenic differentiation of mesenchymal stem cells from human amniotic fluid and human bone marrow: a comparative study. Cell Biol Int 2008;32(11):1439-48. google scholar
  • Chen L, Tredget EE, Liu C, Wu Y. Analysis of allogenicity of mesenchymal stem cells in engraftment and wound healing in mice. PLoS One 2009;4:e7119. doi: 10.1371/journal.pone.0007119 google scholar
  • De Miguel MP, Fuentes-Julian S, Blazquez-Martinez A, Pascual CY, Aller MA, Arias J, et al. Immuno-suppressive properties of mesenchymal stem cells: Advances and applications. Curr Mol Med 2012;12(5):574-91. google scholar
  • Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat. Rev Immunol 2008;8(9):726-36. google scholar
  • Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 2006;24(2):386-98. google scholar
  • Kogler G, Radke TF, Lefort A, Sensken S, Fischer J, Sorg RV, et al. Cytokine production and hematopoiesis supporting activity of cord blood-derived unrestricted somatic stem cells. Exp Hematol 2005;33(5):573-83. google scholar
  • Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells 2008;26(1):212-22. google scholar
  • 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):3838-43. google scholar
  • Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, Dazzi F. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003;101(9):3722-9. google scholar
  • Di Ianni M, Del Papa B, De Ioanni M, Moretti L, Bonifacio E, Cecchini D, et al. Mesenchymal cells recruit and regulate T regulatory cells. Exp Hematol 2008;36(3):309-18. google scholar
  • Bieback K, Kern S, Klüter H, Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 2004;22(4):625-34. google scholar
  • Zeddou M, Briquet A, Relic B, Josse C, Malaise MG, Gothot A, et al. The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood. Cell Biol Int 2010;34(7):693-701. google scholar
  • Galipeau J, Sensebe L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell 2018;22(6):824-33. google scholar
  • Weiss ARR, Dahlke MH. Immunomodulation by mesenchymal stem cells (MSCs): Mechanisms of action of living, apoptotic, and dead mscs. Front Immunol 2019;10:1191. google scholar
  • Kim JH, Jo CH, Kim HR, Hwang YI. Comparison of immunological characteristics of mesenchymal stem cells from the periodontal ligament, umbilical cord, and adipose tissue. Stem Cells Int 2018;8429042. google scholar
  • Inoue S, Popp FC, Koehl GE, Piso P, Schlitt HJ, Geissler EK, et al. Immunomodulatory effects of mesenchymal stem cells in a rat organ transplant model. Transplantation 2006;81(11):1589-95. google scholar
  • Sudres M, Norol F, Trenado A, Gregoire S, Charlotte F, Levacher B, et al. Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J Immunol 2006;176(12):7761-7. google scholar

KORDON KANI VE WHARTON JELİ KAYNAKLI MEZENKİMAL KÖK HÜCRELERİN İMMUNOMODÜLATÖR ÖZELLİKLERİNİN KARŞILAŞTIRILMASI

Year 2023, Volume: 6 Issue: 2, 136 - 142, 26.06.2023
https://doi.org/10.26650/JARHS2023-1216719

Abstract

Amaç: Mezenkimal kök hücreler (MKH’ler), immün düzenleyici özellikleri nedeniyle bir çok immün sistem ilişkili hastalık için tedavi seçeneği olarak umut vaad etmektedir. Wharton Jeli (WJ-MKH) ve kordon kanı (KK-MKH), diğer MKH kaynaklarına göre son dönemlerde daha çok ilgi görmektedir. Çalışmada, WJ-MKH’ler ve KK-MKH’lerin immünolojik etkilerinin mekanizmalarındaki farkı araştırmak amaçlanmıştır.
Gereç ve Yöntem: Periferik kan mononükler hücreler (PKMH) ve MKH ko-kültür öncesi ve sonrası CD4+ T hücrelerin hücre içi sitokin seviyeleri (Interlökin-4 (IL-4), Interferon-γ (IFN-γ), and Interlökin-17 (IL-17)) flow sitometri ile tespit edildi. Aynı zamanda Tümör büyüme faktörü (TGF)-β, IL-4, IL-17, IFN-γ süpernatant sitokin seviyeleri ELISA ile ölçüldü. Çalışmada, ko-kültür MKH/PKMH 1/5 ve 1/10 oranlarında, 24 saat ve 72 saat inkübasyon süreleri uygulandı.
Bulgular: Verilerimiz WJ-MKH’lerin ve KK-MKH’lerin farklı morfolojik özellikleri, çoğalma kapasiteleri, çoğalma süreleri ve immünomodülasyon yetenekleri olduğunu gösterdi. IFN-γ, KK-MKH/PKMH ko-kültür sonrası WJ-MKH/PKMH ko-kültürü sonrasına göre hücre içerisinde hem 1/5 hem 1/10 oranlarında 24. saatlerde anlamlı derecede azalırken, 72. saatlerde anlamlı derecede arttı (p<0,05). IL-17 sitokinin için farklı olarak sadece 72. saatte KK-MKH grubunda WJ-MKH grubuna göre anlamlı derecede hücre içi seviyesi düştü. IL-4 için KK-MKH grubunda 1/10 oran 24 saatte hücre içi seviyesi anlamlı derecede düşerken diğer tüm gruplarda artış gösterdi. KK-MKH/PKMH ko-kültür sonrası TGF-β supernatant seviyesi 1/5 oranında 24 saatte azalırken 72 saatte artış gösterdi. 1/10 oranlarında ise tam tersi 24. saatte KK-MKH grubunda artarken 72 saatlerde anlamlı derecede azaldı (p<0,05).
Sonuç: KK-MKH‘ler ve WJ-MKH’ler, farklı immünmodülatör özellikler göstermektedir. Bu bulgular, KK-MKH’lerin izolasyonun, çoğalma kapasitesinin ve immünmodülatör özelliklerinin farklı olması sebebiyle hücre tedavileri açısından WJ-MKH’lerin kullanılmasının daha avantajlı olduğu söylenebilir.

References

  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006;8(4):315-7. google scholar
  • Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004;363(9419):1439-41. google scholar
  • Atala A. Recent developments in tissue engineering and regenerative medicine. Curr Opin Pediatr 2006;18(2):167-71. google scholar
  • Stenderup K, Justesen J, Clausen C, Kassem M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 2003;33(6):919-26. google scholar
  • Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006;24(5):1294-301. google scholar
  • Zheng YB, Gao ZL, Xie C, Zhu HP, Peng L, Chen JH, et al. Characterization and hepatogenic differentiation of mesenchymal stem cells from human amniotic fluid and human bone marrow: a comparative study. Cell Biol Int 2008;32(11):1439-48. google scholar
  • Chen L, Tredget EE, Liu C, Wu Y. Analysis of allogenicity of mesenchymal stem cells in engraftment and wound healing in mice. PLoS One 2009;4:e7119. doi: 10.1371/journal.pone.0007119 google scholar
  • De Miguel MP, Fuentes-Julian S, Blazquez-Martinez A, Pascual CY, Aller MA, Arias J, et al. Immuno-suppressive properties of mesenchymal stem cells: Advances and applications. Curr Mol Med 2012;12(5):574-91. google scholar
  • Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat. Rev Immunol 2008;8(9):726-36. google scholar
  • Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 2006;24(2):386-98. google scholar
  • Kogler G, Radke TF, Lefort A, Sensken S, Fischer J, Sorg RV, et al. Cytokine production and hematopoiesis supporting activity of cord blood-derived unrestricted somatic stem cells. Exp Hematol 2005;33(5):573-83. google scholar
  • Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells 2008;26(1):212-22. google scholar
  • 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):3838-43. google scholar
  • Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, Dazzi F. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003;101(9):3722-9. google scholar
  • Di Ianni M, Del Papa B, De Ioanni M, Moretti L, Bonifacio E, Cecchini D, et al. Mesenchymal cells recruit and regulate T regulatory cells. Exp Hematol 2008;36(3):309-18. google scholar
  • Bieback K, Kern S, Klüter H, Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 2004;22(4):625-34. google scholar
  • Zeddou M, Briquet A, Relic B, Josse C, Malaise MG, Gothot A, et al. The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood. Cell Biol Int 2010;34(7):693-701. google scholar
  • Galipeau J, Sensebe L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell 2018;22(6):824-33. google scholar
  • Weiss ARR, Dahlke MH. Immunomodulation by mesenchymal stem cells (MSCs): Mechanisms of action of living, apoptotic, and dead mscs. Front Immunol 2019;10:1191. google scholar
  • Kim JH, Jo CH, Kim HR, Hwang YI. Comparison of immunological characteristics of mesenchymal stem cells from the periodontal ligament, umbilical cord, and adipose tissue. Stem Cells Int 2018;8429042. google scholar
  • Inoue S, Popp FC, Koehl GE, Piso P, Schlitt HJ, Geissler EK, et al. Immunomodulatory effects of mesenchymal stem cells in a rat organ transplant model. Transplantation 2006;81(11):1589-95. google scholar
  • Sudres M, Norol F, Trenado A, Gregoire S, Charlotte F, Levacher B, et al. Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J Immunol 2006;176(12):7761-7. google scholar
There are 22 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Articles
Authors

Ayşe Erol 0000-0003-4454-4651

Figen Abatay Sel 0000-0002-1155-1284

Mediha Süleymanoğlu 0000-0002-1401-4863

Gökhan Demirayak 0000-0002-5679-3199

Dürdane Serap Kuruca 0000-0001-7878-9994

Fatma Savran Oğuz 0000-0002-6018-8936

Publication Date June 26, 2023
Submission Date December 9, 2022
Published in Issue Year 2023 Volume: 6 Issue: 2

Cite

MLA Erol, Ayşe et al. “COMPARISON OF THE IMMUNOMODULATORY PROPERTIES OF THE CORD BLOOD AND WHARTON’S JELLY DERIVED MESENCHYMAL STEM CELLS”. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, vol. 6, no. 2, 2023, pp. 136-42, doi:10.26650/JARHS2023-1216719.