Growth suppression effect of human mesenchymal stem cells from bone marrow, adipose tissue, and Wharton's jelly of umbilical cord on PBMCs

Document Type : Original Article

Authors

1 Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Laboratory for Stem Cell Research, Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Objective(s):Immunosuppressive property of mesenchymal stem cells (MSCs) has great attraction in regenerative medicine especially when dealing with tissue damage involving immune reactions. The most attractive tissue sources of human MSCs used in clinical applications are bone marrow (BM), adipose tissue (AT), and Wharton's jelly (WJ) of human umbilical cord. The current study has compared immunomodulatory properties of human BM, AT, and WJ-MSCs.
Materials and Methods: Three different types of human MSCs were isolated, cultured, and characterized by flow cytometry and differentiation potentials. The MSCs were co-cultured with allogeneic phytohemagglutinin (PHA) activated peripheral blood mononuclear cells (PBMCs). The proliferation of PBMCs was assessed by flow cytometry of carboxyfluorescein succinimidyl ester (CFSE) stained cells and compared to each other and to the growth of PBMCs in the absence of MSCs, 3 days post co-culture. Additionally, the growth suppression was indirectly assessed by using the transwell culture system.
Results: the proliferation of PBMCs reduced to 6.2, 7 and 15.4- fold in cultures with AT-MSCs, WJ-MSCs, and BM-MSCs, respectively, compared to the PHA-activated cells. When the growth suppression was indirectly assessed by using the transwell culture system, it was revealed that AT-MSCs, WJ-MSCs, and BM-MSCs caused growth reduction in PBMCs to 3, 8, and 8 -fold, respectively, compared to the PHA-activated cells.
Conclusion:These data collectively conclude that the immunomodulatory effects of MSCs, which may mostly carry out through direct cell to cell contact, are different between various sources. Accordingly results of this study may contribute to the application of these cells in cell therapy and regenerative medicine.

Keywords


1. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 2007; 25: 2739-2749.
2. Mareschi K, Ferrero I, Rustichelli D, Aschero S, Gammaitoni L, Aglietta M, et al. Expansion of mesenchymal stem cells isolated from pediatric and adult donor bone marrow. J Cell Biochem 2006; 97:744-754.
3. Mitchell KE, Weiss ML, Mitchell BM, Martin P, Davis D, Morales L, et al. Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells 2003; 21:50–60.
4. Friedenstein AJ, Gorskaja UF, Julagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs.  Exp Hematol 1976; 4:267–274.
5. Ankrum J, Karp JM. Mesenchymal stem cell therapy: Two steps forward, one step back.  Trends Mol Med 2010; 16:203–209.
6. Kassem M, Kristiansen M, Abdallah BM. Mesenchymal stem cells: cell biology and potential use in therapy. Basic Clin Pharmacol Toxicol 2004; 95:209–214.
7. Docheva D, Popov C, Mutschler W, Schieker M. Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system. J Cell Mol Med 2007; 11:21-38.
8. Nardi NB, Meirelles SD. Mesenchymal stem cells: isolation, in vitro expansion and characterization. HEP 2006; 174:249–282.
9. Kim N, Cho SG. Clinical applications of mesenchymal stem cells. Korean J Intern Med 2013; 28:387-402.
10. Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anerg. Blood 2005; 106:1755–1761.
11. Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA 2003; 100:8407–8411.
12. Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E, et al. IFN-c activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol 2008; 38:1745–1755.
13. Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum 2005; 52:2521-2529.
14. Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 2000; 109:235-242.
15. Musina RA, Bekchanova ES, Sukhikh GT. Comparison of mesenchymal stem cells obtained from different human tissues. Bull Exp Biol Med 2005; 139:504-509.
16. Jurgens WJ, Oedayrajsingh-Varma MJ, Helder MN, Zandiehdoulabi B, Schouten TE, Kuik DJ, et al. Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies. Cell Tissue Res 2008; 332:415–426.
17. Sarugaser R, Lickorish D, Baksh D, Hosseini MM, Davies JE. Human umbilical cord perivascular (HUCPV) cells: A source of mesenchymal progenitors. Stem Cells 2005; 23:220–229.
18. Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 2004; 22:1330–1337.
19. Ayatollahi M, Soleimani M, Geramizadeh B, Imanieh MH. Insulin-like growth factor1 (IGF-I) improves hepatic differentiation of human bone marrow-derived mesenchymal stem cells. Cell Biol Int 2011; 35:1169-1176.
20. Razmkhah M, Abedi N, Hosseini A, Imani MT, Talei AR, Ghaderi A. Induction of T regulatory subsets from Naïve CD4+ T cells after exposure to breast cancer adipose derived stem cells. Iran J Immunol 2015; 12:1-15.
21.  Rezaeifard S, Razmkhah M, Robati M, Momtahan M, Ghaderi A. Adipose derived stem cells isolated from omentum: a novel source of chemokines for ovarian cancer growth. J Cancer Res Ther 2014; 10:159-164.
22. Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K, et al. Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 2003; 24:3531-3541.
23. Shang Q, Wang Z, Liu W, Shi Y, Cui L, Cao Y. Tissue-engineered bone repair of sheep cranial defects with autologous bone marrow stromal cells. J Craniofac Surg 2001; 12:586–593.
24. Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 2001; 103:2776–2779.
25. Noort WA, Kruisselbrink AB, In’t Anker PS, Kruger M, van Bezooijen RL, de Paus RA, et al. Mesenchymal stem cells promote engraftment of human umbilical cord blood derived CD34(+) cells in NOD/SCID mice. Exp Hematol 2002; 30:870–878.
26. 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; 363:1439-1441.
27. Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Hematol 2000; 109:235–242.
28. Strioga M, Viswanathan S, Darinskas A, Slaby O, Michalek J. Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev 2012; 21:2724-2752.
29. Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB. Pro-inflammatory cytokines, IFNgamma and TNFalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PLoS One 2010; 5:e9016.
30. Amable PR, Teixeira MV, Carias RB, Granjeiro JM, Borojevic R. Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton's jelly. Stem Cell Res Ther 2014; 5:53.
31. Ribeiro A, Laranjeira P, Mendes S, Velada I, Leite C, Andrade P, et al. Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem Cell Res Ther 2013; 4:125.
32. Bochev I, Elmadjian G, Kyurkchiev D, Tzvetanov L, Altankova I, Tivchev P, et al. Mesenchymal stem cells from human bone marrow or adipose tissue differently modulate mitogen-stimulated B-cell immunoglobulin production in vitro. Cell Biol Int 2008; 32:384–393.
33. Ivanova-Todorova E, Bochev I, Mourdjeva M, Dimitrov R, Bukarev D, Kyurkchiev S, et al. Adipose tissue-derived mesenchymal stem cells are more potent suppressors of dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells. Immunol Lett 2009; 126:37–42.
34. Najar M, Raicevic G, Jebbawi F, De Bruyn C, Meuleman N, Bron D, et al. Characterization and functionality of the CD200-CD200R system during mesenchymal stromal cell interactions with T-lymphocytes. Immunol Lett 2012; 146:50-56.