The source of human mesenchymal stromal cells influences their TLR profile as well as their functional properties

Raicevic, Gordana; Najar, Mehdi; Stamatopoulos, Basile; Bruyn, Cécile De; Meuleman, Nathalie; Bron, Dominique; Toungouz, Michel; Lagneaux, Laurence

doi:10.1016/j.cellimm.2011.05.010

Cited by 141 publications

(138 citation statements)

References 57 publications

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“…The functions of adult MSCs, such as hBW-MSCs and hAT-MSCs, were modulated by the TLR4-LPS signalling pathway ex vivo , and LPS stimulation resulted in the increased production of such inflammatory cytokines and chemokines as IL-1β, IL-6, and IL-8 [17,23,24,25,28]. However, for the role of TLR4 in hWJ-MSCs, two early reports came to the opposite conclusion [27,29]. Raicevic et al explored the details of the hWJ-MSCs TLRs expression profiles and found that TLR4 is not expressed in these cells at transcription level or protein level and consequently do not respond to LPS activation [29].…”

Section: Discussionmentioning

confidence: 99%

“…However, for the role of TLR4 in hWJ-MSCs, two early reports came to the opposite conclusion [27,29]. Raicevic et al explored the details of the hWJ-MSCs TLRs expression profiles and found that TLR4 is not expressed in these cells at transcription level or protein level and consequently do not respond to LPS activation [29]. In contrast, report by Chen et al demonstrated the presence of TLR4 on the surface of human umbilical cord-derived MSCs (hUC-MSCs) at a very low level (5%-6%) by flow cytometry analysis but further confirmed that LPS engagement induced NF-NκB translocation and resulted in the up-regulation of IL-6, IL-8, and IFN-γ mRNA expression in hUC-MSCs, which indicated TLR4 is a functional receptor [27].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the TLR profiles in hMSCs derived from various tissues (including hWJ-MSCs) have been explored, and their regulatory effects on MSC differentiation, proliferation, and immunomodulation have been described [23,24,25,26,27]. However, MSCs derived from various sources display different TLRs profiles, functional properties, and responses to stimulation by TLRs' agonists [23,24,25,26,27,28,29]. …”

Section: Introductionmentioning

confidence: 99%

“…It has been used to investigate the response of human adipose tissue-derived MSCs (hAD-MSCs), hBW-MSCs, and human cord blood-derived MSCs (hCB-MSCs) to TLR4 triggering ex vivo , and it was found that TLR4 expressed at a high level and is a functional receptor in these cells [23,25,26]. In contrast, the presence and functional properties of TLR4 in hWJ-MSCs remains controversial [27,29]. Therefore, this study aimed to investigate the expression profile of TLR4 in hWJ-MSCs and to evaluate the inductive effect of TLR4 agonist on the proliferation, apoptosis, paracrine profiles, and immunosuppressive properties of hWJ-MSCs.…”

Section: Introductionmentioning

confidence: 99%

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Lipopolysaccharides Shapes the Human Wharton's Jelly-Derived Mesenchymal Stem Cellsin Vitro

Mei¹,

Zhou²,

Zhang³

et al. 2013

Cell Physiol Biochem

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Background: Although the expression of toll-like receptors (TLRs) on different types of human mesenchymal stem cells (hMSCs) has recently been reported, controversy remains regarding the presence of TLR4 as well as its engagement and impact on human Wharton's jelly-derived MSCs (hWJ-MSCs). Methods: In the present study, the expression and role of TLR4 in hWJ-MSCs was investigated using a model of lipopolysaccharide (LPS). Proliferation, apoptosis, and the expression of paracrine factors in hWJ-MSCs primed with LPS were analysed. Results: The expression of TLR4 was high at the RNA level but very low at the protein level. hWJ-MSCs responded to LPS stimulation and initiated a marked up-regulation of inflammatory cytokine (IL-1α, IL-1β, IL-6, and IL-8) production. Moreover, hWJ-MSCs LPS stimulation resulted in the up-regulation of indoleamine 2,3-dioxygenase [IDO]-1, Cox2, interferon [IFN]-β, and matrix metalloproteinase (MMP)-2 but a down-regulation of MMP-9, which affect the immunosuppressive potential of hWJ-MSCs. Conclusions: These data suggest that LPS engagement shapes hWJ-MSCs and results in the production of pro-inflammatory cytokines and inhibitory immune mediators, showing TLR4 agonist induces the hWJ-MSCs polarization to a pro-inflammatory and immunosuppressive state, which may be beneficial for the exploration of the clinical potential of hWJ-MSCs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lipopolysaccharides Shapes the Human Wharton's Jelly-Derived Mesenchymal Stem Cellsin Vitro

Mei¹,

Zhou²,

Zhang³

et al. 2013

Cell Physiol Biochem

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show abstract

“…In particular, we and others highlighted the expression of immunomodulatory molecules such as HLA-G, HLA-E, PGE2 and HGF in WJ-MSC [12,28,29]. The non-classical type I HLA molecules are involved in the induction of tolerance of NK-cells towards self cells.…”

Section: Introductionmentioning

confidence: 99%

Perinatal and Wharton's Jelly-Derived Mesenchymal Stem Cells in Cartilage Regenerative Medicine and Tissue Engineering Strategies

Iacono

Anzalone

Corrao

et al. 2011

TOTERMJ

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Stem cells can be found in embryonic and extraembryonic tissues as well as in adult organs. In particular, research in the last few years has delineated the key features of perinatal stem cells derived from fetus-associated tissues. These cells show multiple differentiation potential, can be easily expanded ex vivo, and raise no ethical concerns as regards their use. Several reports indicate that cells isolated from Wharton's jelly (WJ), the main component of umbilical cord extracellular matrix, are multipotent stem cells that express markers shared by other mesenchymal stem cells (MSC) and give rise to different mature cell types belonging to all three germ layers. Moreover, WJ-MSC display promising hypoimmunogenic and immunomodulatory properties, since they express molecules able to modulate NK cells and expand regulatory T-cell populations.In this review, we focus on the use of perinatal stem cells for regenerative medicine aimed at cartilage repair and regeneration. Cartilage is a specialized connective tissue which has poor regeneration and self-repair capacity in vivo. Traumatic injury or autoimmune processes are among the main causes of cartilage damage and degeneration, for which new hope comes from tissue engineering using stem cells which have undergone chondrocyte-like differentiation. We analyze the in vitro and in vivo data on the use of perinatal stem cells, in particular WJ-MSC, for cartilage regenerative medicine. The high variability of cell sources, the use of different types of scaffolds and matrixes, and the administration of several combinations of growth factors clearly point out the need for further research to optimize this cellular therapy approach and translate the results obtained from bench to clinic.

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Wharton's Jelly Mesenchymal Stem Cells and Immune Modulation: Regenerative Medicine Meets Tissue Repair

Anzalone

Farina

Iacono

et al. 2013

Perinatal Stem Cells

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The source of human mesenchymal stromal cells influences their TLR profile as well as their functional properties

Cited by 141 publications

References 57 publications

Lipopolysaccharides Shapes the Human Wharton's Jelly-Derived Mesenchymal Stem Cellsin Vitro

Lipopolysaccharides Shapes the Human Wharton's Jelly-Derived Mesenchymal Stem Cellsin Vitro

Perinatal and Wharton's Jelly-Derived Mesenchymal Stem Cells in Cartilage Regenerative Medicine and Tissue Engineering Strategies

Wharton's Jelly Mesenchymal Stem Cells and Immune Modulation: Regenerative Medicine Meets Tissue Repair

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