Comprehensive characterization of four different populations of human mesenchymal stem cells as regards their immune properties, proliferation and differentiation

Li,Xiuying; Bai,Jinping; Ji,Xiaofeng; Li,Ronggui; Xuan,Yali; Wang,Yimin

doi:10.3892/ijmm.2014.1821

Comprehensive characterization of four different populations of human mesenchymal stem cells as regards their immune properties, proliferation and differentiation

Authors:
- Xiuying Li
- Jinping Bai
- Xiaofeng Ji
- Ronggui Li
- Yali Xuan
- Yimin Wang
View Affiliations

Affiliations: The Central Laboratory, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Department of Pathology, Jilin University, The Key Laboratory of Pathobiology, Ministry of Education, Changchun, Jilin 130021, P.R. China, Department of Orthopedics, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Jilin Zhongke Bio-engineering, Co., Ltd., Changchun, Jilin 130012, P.R. China
Published online on: June 25, 2014 https://doi.org/10.3892/ijmm.2014.1821
Pages: 695-704
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In the present study, we compared mesenchymal stem cells (MSCs) derived from 4 different sources, human bone marrow (BM), adipose tissue (AT), umbilical cord Wharton's Jelly (WJ) and the placenta (PL), in order to determine which population of MSCs displayed the most prominent immunosuppressive effects on phytohemagglutinin-induced T cell proliferation, and which one had the highest proliferative and differentiation potential. MSC and T lymphocyte co-culture (mixed culture) was used to determine whether the MSCs inhibit T cell proliferation, as well as which population of MSCs has the strongest inhibitory ability. The expression of immune-related genes was analyzed by RT-PCR and RT-qPCR. The proliferation and differentiation potential of the MSCs were determined using standard methods. Following MSC and T cell co-culture, mitogen-induced T cell proliferation was effectively suppressed by all 4 populations of MSCs. This occurred through soluble factors rather than direct contact inhibition. Among the 4 populations of MSCs, the WJ-MSC has the strongest suppression effects. On immune related genes, WJ-MSC has the weakest expression of MHC II genes, TLR4, TLR3, JAG1, NOTCH2 and NOTCH3. To compare the proliferation potential, WJ-MSCs showed the most rapid growth rate followed by the AT-, PL- and BM-MSCs. As regards differentiation potential, the WJ-MSCs had the strongest osteogenetic ability followed by PL, AT and BM-MSC. AT-MSC has the strongest adipogenetic ability followed by the WJ-, BM- and PL-MSCs. These data indicated that the WJ-MSCs had the strongest immunomodulatory and immunosuppressive potential. In light of these observations, we suggest that WJ-MSCs are the most attractive cell population for use in immune cellular therapy when immunosuppressive action is required.

View Figures

View References

1	Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF and Keiliss-Borok IV: Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation. 17:331–340. 1974. View Article : Google Scholar : PubMed/NCBI
2	Caplan AI: Mesenchymal stem cells. J Orthop Res. 9:641–650. 1991. View Article : Google Scholar : PubMed/NCBI
3	Kopen GC, Prockop DJ and Phinney DG: Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA. 96:10711–10716. 1999. View Article : Google Scholar
4	Pittenger MF, Mackay AM, Beck SC, et al: Multilineage potential of adult human mesenchymal stem cells. Science. 284:143–147. 1999. View Article : Google Scholar : PubMed/NCBI
5	Beltrami AP, Cesselli D, Bergamin N, et al: Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow). Blood. 110:3438–3446. 2007. View Article : Google Scholar : PubMed/NCBI
6	Fan CG, Zhang QJ and Zhou JR: Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord. Stem Cell Rev. 7:195–207. 2011. View Article : Google Scholar : PubMed/NCBI
7	Mosna F, Sensebe L and Krampera M: Human bone marrow and adipose tissue mesenchymal stem cells: a user’s guide. Stem Cells Dev. 19:1449–1470. 2010.
8	Friedenstein AJ, Petrakova KV, Kurolesova AI and Frolova GP: Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 6:230–247. 1968.PubMed/NCBI
9	Tondreau T, Meuleman N, Delforge A, et al: Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood: proliferation, Oct4 expression, and plasticity. Stem Cells. 23:1105–1112. 2005. View Article : Google Scholar : PubMed/NCBI
10	Zuk PA, Zhu M, Mizuno H, et al: Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7:211–228. 2001. View Article : Google Scholar : PubMed/NCBI
11	Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I and Fisk NM: Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 98:2396–2402. 2001. View Article : Google Scholar : PubMed/NCBI
12	Keating A: Mesenchymal stromal cells. Curr Opin Hematol. 13:419–425. 2006. View Article : Google Scholar
13	Friedenstein AJ, Chailakhjan RK and Lalykina KS: The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 3:393–403. 1970.PubMed/NCBI
14	Friedenstein AJ, Gorskaja JF and Kulagina NN: Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol. 4:267–274. 1976.PubMed/NCBI
15	Grassel S, Stockl S and Jenei-Lanzl Z: Isolation, culture, and osteogenic/chondrogenic differentiation of bone marrow-derived mesenchymal stem cells. Methods Mol Biol. 879:203–267. 2012. View Article : Google Scholar : PubMed/NCBI
16	Eslaminejad MB, Mirzadeh H, Mohamadi Y and Nickmahzar A: Bone differentiation of marrow-derived mesenchymal stem cells using beta-tricalcium phosphate-alginate-gelatin hybrid scaffolds. J Tissue Eng Regen Med. 1:417–424. 2007. View Article : Google Scholar : PubMed/NCBI
17	Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L and Verfaillie CM: Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood. 98:2615–2625. 2001. View Article : Google Scholar
18	Tomic S, Djokic J, Vasilijic S, et al: Immunomodulatory properties of mesenchymal stem cells derived from dental pulp and dental follicle are susceptible to activation by toll-like receptor agonists. Stem Cells Dev. 20:695–708. 2011. View Article : Google Scholar : PubMed/NCBI
19	Toubai T, Paczesny S, Shono Y, et al: Mesenchymal stem cells for treatment and prevention of graft-versus-host disease after allogeneic hematopoietic cell transplantation. Curr Stem Cell Res Ther. 4:252–259. 2009. View Article : Google Scholar : PubMed/NCBI
20	Tse WT, Pendleton JD, Beyer WM, Egalka MC and Guinan EC: Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation. 75:389–397. 2003. View Article : Google Scholar : PubMed/NCBI
21	Ramasamy R, Tong CK, Seow HF, Vidyadaran S and Dazzi F: The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function. Cell Immunol. 251:131–136. 2008. View Article : Google Scholar : PubMed/NCBI
22	Che N, Li X, Zhou S, et al: Umbilical cord mesenchymal stem cells suppress B-cell proliferation and differentiation. Cell Immunol. 274:46–53. 2012. View Article : Google Scholar : PubMed/NCBI
23	Spaggiari GM, Capobianco A, Becchetti S, Mingari MC and Moretta L: Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood. 107:1484–1490. 2006. View Article : Google Scholar : PubMed/NCBI
24	Deuse T, Stubbendorff M, Tang-Quan K, et al: Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells. Cell Transplant. 20:655–667. 2011. View Article : Google Scholar : PubMed/NCBI
25	Najar M, Raicevic G, Id Boufker H, et al: Modulated expression of adhesion molecules and galectin-1: role during mesenchymal stromal cell immunoregulatory functions. Exp Hematol. 38:922–932. 2010. View Article : Google Scholar : PubMed/NCBI
26	De Bruyn C, Najar M, Raicevic G, et al: A rapid, simple, and reproducible method for the isolation of mesenchymal stromal cells from Wharton’s jelly without enzymatic treatment. Stem Cells Dev. 20:547–557. 2011.
27	Battula VL, Bareiss PM, Treml S, et al: Human placenta and bone marrow derived MSC cultured in serum-free, b-FGF-containing medium express cell surface frizzled-9 and SSEA-4 and give rise to multilineage differentiation. Differentiation. 75:279–291. 2007. View Article : Google Scholar : PubMed/NCBI
28	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
29	Young RG, Butler DL, Weber W, Caplan AI, Gordon SL and Fink DJ: Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. J Orthop Res. 16:406–413. 1998. View Article : Google Scholar : PubMed/NCBI
30	Wakitani S, Saito T and Caplan AI: Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve. 18:1417–1426. 1995. View Article : Google Scholar : PubMed/NCBI
31	Parker AM and Katz AJ: Adipose-derived stem cells for the regeneration of damaged tissues. Expert Opin Biol Ther. 6:567–578. 2006. View Article : Google Scholar : PubMed/NCBI
32	Kobayashi K, Kubota T and Aso T: Study on myofibroblast differentiation in the stromal cells of Wharton’s jelly: expression and localization of alpha-smooth muscle actin. Early Hum Dev. 51:223–233. 1998.PubMed/NCBI
33	Wulf GG, Viereck V, Hemmerlein B, et al: Mesengenic progenitor cells derived from human placenta. Tissue Eng. 10:1136–1147. 2004. View Article : Google Scholar : PubMed/NCBI
34	Chen MY, Lie PC, Li ZL and Wei X: Endothelial differentiation of Wharton’s jelly-derived mesenchymal stem cells in comparison with bone marrow-derived mesenchymal stem cells. Exp Hematol. 37:629–640. 2009.
35	Baksh D, Yao R and Tuan RS: Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells. 25:1384–1392. 2007. View Article : Google Scholar : PubMed/NCBI
36	Raynaud CM, Maleki M, Lis R, et al: Comprehensive characterization of mesenchymal stem cells from human placenta and fetal membrane and their response to osteoactivin stimulation. Stem Cells Int. 2012:6583562012. View Article : Google Scholar : PubMed/NCBI
37	Zhu SF, Zhong ZN, Fu XF, et al: Comparison of cell proliferation, apoptosis, cellular morphology and ultrastructure between human umbilical cord and placenta-derived mesenchymal stem cells. Neurosci Lett. 541:77–82. 2013. View Article : Google Scholar
38	Stenderup K, Justesen J, Clausen C and Kassem M: Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone. 33:919–926. 2003. View Article : Google Scholar : PubMed/NCBI
39	Post S, Abdallah BM, Bentzon JF and Kassem M: Demonstration of the presence of independent pre-osteoblastic and pre-adipocytic cell populations in bone marrow-derived mesenchymal stem cells. Bone. 43:32–39. 2008. View Article : Google Scholar : PubMed/NCBI
40	Larsen KH, Frederiksen CM, Burns JS, Abdallah BM and Kassem M: Identifying a molecular phenotype for bone marrow stromal cells with in vivo bone-forming capacity. J Bone Miner Res. 25:796–808. 2010.PubMed/NCBI
41	De Ugarte DA, Morizono K, Elbarbary A, et al: Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs. 174:101–109. 2003.PubMed/NCBI
42	Lorenz K, Sicker M, Schmelzer E, et al: Multilineage differentiation potential of human dermal skin-derived fibroblasts. Exp Dermatol. 17:925–932. 2008. View Article : Google Scholar : PubMed/NCBI
43	Kern S, Eichler H, Stoeve J, Kluter H and Bieback K: Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 24:1294–1301. 2006. View Article : Google Scholar
44	Zhang X, Hirai M, Cantero S, et al: Isolation and characterization of mesenchymal stem cells from human umbilical cord blood: reevaluation of critical factors for successful isolation and high ability to proliferate and differentiate to chondrocytes as compared to mesenchymal stem cells from bone marrow and adipose tissue. J Cell Biochem. 112:1206–1218. 2011.
45	Dazzi F and Krampera M: Mesenchymal stem cells and autoimmune diseases. Best Pract Res Clin Haematol. 24:49–57. 2011. View Article : Google Scholar
46	Kebriaei P and Robinson S: Treatment of graft-versus-host-disease with mesenchymal stromal cells. Cytotherapy. 13:262–268. 2011. View Article : Google Scholar : PubMed/NCBI
47	Kode JA, Mukherjee S, Joglekar MV and Hardikar AA: Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration. Cytotherapy. 11:377–391. 2009. View Article : Google Scholar : PubMed/NCBI
48	Krampera M, Glennie S, Dyson J, et al: Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood. 101:3722–3729. 2003. View Article : Google Scholar
49	Polchert D, Sobinsky J, Douglas G, et al: IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol. 38:1745–1755. 2008. View Article : Google Scholar : PubMed/NCBI
50	Rubinstein P, Rosenfield RE, Adamson JW and Stevens CE: Stored placental blood for unrelated bone marrow reconstitution. Blood. 81:1679–1690. 1993.PubMed/NCBI
51	Augello A, Tasso R, Negrini SM, et al: Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol. 35:1482–1490. 2005. View Article : Google Scholar : PubMed/NCBI
52	Yang SH, Park MJ, Yoon IH, et al: Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10. Exp Mol Med. 41:315–324. 2009. View Article : Google Scholar : PubMed/NCBI