Abstract
Background aims
Toll-like receptors (TLRs) play an important role in innate and adaptive immunity
by recognizing pathogen-associated molecular patterns (PAMPs).
Methods
In the present study, we investigated the expression and role of TLRs on human umbilical
cord mesenchymal stromal cells (UC-MSCs). The proliferation, differentiation and immunoregulatory
activity of UC-MSCs primed with or without TLR ligands were determined.
Results
At the RNA level, the expression of TLR2, 4, 6 and 9 was relatively higher than that
of other TLRs. However, TLR3 and TLR4 expression were relatively higher at the protein
level. UC-MSCs expressed functional TLRs by nuclear factor-κB activation and cytokine
expression assay. Poly-inosinic acid:cytidylic acid [Poly(I:C)] stimulation inhibited
the proliferation of UC-MSCs, but the ligand of other TLRs had no significant effect.
Poly(I:C) stimulation enhanced the adipogenic differentiation capability of UC-MSCs,
but lipopolysaccharide inhibited the adipogenic differentiation. Poly(I:C) and CpG-oligonucleotide
promoted the immunosuppressive potentiality of UC-MSCs, accompanied with the phosphorylation
of interferon regulatory factor 3 (IRF3) and increased expression of indoleamine 2,3-dioxygenase
and interferon β, whereas activation of other TLR ligands (synthetic analog fibroblast-stimulating
lipopeptide-1 and lipopolysaccharide) failed to affect the immunoregulatory activity
of UC-MSCs.
Conclusions
Taken together, our data demonstrated that TLR activation influenced the function
of UC-MSCs, which might have important implications in future efforts to explore the
clinical potentials of UC-MSCs.
Key Words
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References
- Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy.J Cell Mol Med. 2004; 8: 301-316
- Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration.Cytotherapy. 2009; 11: 377-391
- Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-gamma and TNF-alpha.Nat Med. 2011; 17: 1594-1601
- Protective effects of neurotrophic factor-secreting cells in a 6-OHDA rat model of Parkinson disease.Stem Cells Dev. 2009; 18: 1179-1190
- Enhanced hepatic differentiation of mesenchymal stem cells after pretreatment with injured liver tissue.Differentiation. 2011; 81: 42-48
- Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications.Stem Cell Res Ther. 2010; 1: 2
- Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials.Haematologica. 2006; 91: 1017-1026
- Wharton's jelly-derived cells are a primitive stromal cell population.Stem Cells. 2008; 26: 591-599
- Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow.Stem Cells. 2007; 25: 1384-1392
- Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC.Cell Commun Signal. 2011; 9: 12
- Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells.Cell Transplant. 2011; 20: 655-667
- Potential risks of bone marrow cell transplantation into infarcted hearts.Blood. 2007; 110: 1362-1369
- Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease.Stem Cells. 2007; 25: 602-611
- No contribution of umbilical cord mesenchymal stromal cells to capillarization and venularization of hepatic sinusoids accompanied by hepatic differentiation in carbon tetrachloride-induced mouse liver fibrosis.Cytotherapy. 2010; 12: 371-383
- Therapeutic effect of human umbilical cord multipotent mesenchymal stromal cells in a rat model of stroke.Transplantation. 2009; 87: 350-359
- Therapeutic benefit of human umbilical cord derived mesenchymal stromal cells in intracerebral hemorrhage rat: implications of anti-inflammation and angiogenesis.Cell Physiol Biochem. 2009; 24: 307-316
- Intrapulmonary delivery of human umbilical cord mesenchymal stem cells attenuates acute lung injury by expanding CD4+CD25+ Forkhead Boxp3 (FOXP3)+ regulatory T cells and balancing anti- and pro-inflammatory factors.Cell Physiol Biochem. 2011; 27: 587-596
- Improvement in cardiac function following transplantation of human umbilical cord matrix-derived mesenchymal cells.Cardiology. 2011; 120: 9-18
- Islet neogenesis from the constitutively nestin expressing human umbilical cord matrix derived mesenchymal stem cells.Islets. 2010; 2: 112-120
- Mesenchymal stem cells: revisiting history, concepts, and assays.Cell Stem Cell. 2008; 2: 313-319
- Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair–current views.Stem Cells. 2007; 25: 2896-2902
- The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.Nat Immunol. 2010; 11: 373-384
- Modulation of adaptive immunity with Toll-like receptors.Semin Immunol. 2009; 21: 185-193
- Endogenous ligands of Toll-like receptors.J Leukoc Biol. 2004; 76: 514-519
- Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock.Nat Med. 2007; 13: 1042-1049
- Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses.J Exp Med. 2008; 205: 79-90
- Insights into the role of Toll-like receptors in modulation of T cell responses.Cell Tissue Res. 2011; 343: 141-152
- Regulation of antigen uptake, migration, and lifespan of dendritic cell by Toll-like receptors.J Mol Med. 2010; 88: 873-880
- The role of toll-like receptors in chronic inflammation.Int J Biochem Cell Biol. 2010; 42: 506-518
- Toll-like receptor signaling pathways–therapeutic opportunities.Mediators Inflamm. 2010; 2010: 781235
- The application of Toll like receptors for cancer therapy.Int J Biol Sci. 2010; 6: 675-681
- Toll-like receptors and their ligands control mesenchymal stem cell functions.Blood. 2007; 109: 1422-1432
- Toll-like receptor-mediated signaling in human adipose-derived stem cells: implications for immunogenicity and immunosuppressive potential.Tissue Eng Part A. 2009; 15: 1579-1589
- Role of toll-like receptors on human adipose-derived stromal cells.Stem Cells. 2006; 24: 2744-2752
- Toll-like receptor triggering in cord blood mesenchymal stem cells.J Cell Mol Med. 2009; 13: 3415-3426
- Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses.Stem Cells. 2008; 26: 99-107
- Toll-like receptors 3 and 4 are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing Notch signaling.Stem Cells. 2008; 26: 279-289
- Implication of NOD1 and NOD2 for the differentiation of multipotent mesenchymal stem cells derived from human umbilical cord blood.PLoS One. 2010; 5: e15369
- Modulation of adult mesenchymal stem cells activity by toll-like receptors: implications on therapeutic potential.Mediators Inflamm. 2010; 2010: 865601
- Mesenchymal stem cells: mechanisms of immunomodulation and homing.Cell Transplant. 2010; 19: 667-679
- Multipotent stem cells from umbilical cord: cord is richer than blood!.Stem Cells. 2008 Jan; 26: 146-150
- 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. 2011; 20: 695-708
- The source of human mesenchymal stromal cells influences their TLR profile as well as their functional properties.Cell Immunol. 2011; 270: 207-216
- Regulation of XIAP translation and induction by MDM2 following irradiation.Cancer Cell. 2009; 15: 363-375
- The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling.Nat Rev Immunol. 2007; 7: 353-364
- Toll-like receptors mediate proliferation and survival of multiple myeloma cells.Leukemia. 2006; 20: 1138-1144
- The TLR7/8 ligand resiquimod targets monocyte-derived dendritic cell differentiation via TLR8 and augments functional dendritic cell generation.Cell Immunol. 2011; 271: 401-412
- A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype.PLoS One. 2010; 5: e10088
- Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue.Stem Cells. 2006; 24: 1294-1301
- Immunomodulatory properties of mesenchymal stromal cells.Blood. 2007; 110: 3499-3506
- Mesenchymal stem cells induce apoptosis of activated T cells.Leukemia. 2005; 19: 1597-1604
- Human mesenchymal stem cells promote survival of T cells in a quiescent state.Stem Cells. 2007; 25: 1753-1760
- Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism.Clin Immunol. 2010; 135: 448-458
- Toll-like receptor engagement enhances the immunosuppressive properties of human bone marrow-derived mesenchymal stem cells by inducing indoleamine-2,3-dioxygenase-1 via interferon-beta and protein kinase R.Stem Cells. 2009; 27: 909-919
Article info
Publication history
Published online: January 25, 2013
Accepted:
December 10,
2012
Received:
November 23,
2012
Identification
Copyright
© 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
