Toll-like receptor 3 pre-conditioning increases the therapeutic efficacy of umbilical cord mesenchymal stromal cells in a dextran sulfate sodium–induced colitis model

Fuenzalida, Patricia; Kurte, Mónica; Fernández-O'Ryan, Catalina; Ibáñez, Cristina; Gauthier-Abeliuk, Melanie; Vega-Letter, Ana María; González, Paz L.; Irarrázabal, Carlos E.; Quezada, Nataly; Figueroa, Fernando; Carrión, Flavio

doi:10.1016/j.jcyt.2016.02.002

Cited by 45 publications

(45 citation statements)

References 46 publications

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“…Importantly, TLR activation has been implicated in the pathology of various inflammatory diseases including rheumatoid arthritis or inflammatory bowel disease (IBD), since they can either initiate or perpetuate the chronic inflammation due to the continuous exposure to TLR ligands (353637). However, Fuenzalida et al (38) has recently shown that short in vitro TLR3 pre-conditioning with poly(I:C) enhances the therapeutic efficacy of UCMSCs (umbilical cord matrix stem cells), which is a major breakthrough for developing improved treatments for patients with inflammatory bowel disease.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Mesenchymal Stromal Cells and Toll-Like Receptor Priming: A Critical Review

et al. 2017

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Mesenchymal Stromal Cells (MSCs) are potential cellular candidates for several immunotherapy purposes. Their multilineage potential and immunomodulatory properties make them interesting tools for the treatment of various immunological diseases. However, depending on the local microenvironment, diverse biological functions of MSCs can be modulated. Indeed, during infections such as obtained following TLR-agonist engagement (called as TLR priming), the phenotype, multilineage potential, hematopoietic support and immunomodulatory capacity of MSCs can present critical changes, which could further affect their therapeutic potential. Thus, for appropriate clinical application of MSCs, it is important to well know and understand these effects in particular during infectious episodes and to find the suitable experimental settings to study that. Pre-stimulation of MSCs with a specific TLR ligand may serve as an effective priming step to modulate one of its function to achieve a desired therapeutic issue.

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Section: Toll-like Receptorsmentioning

confidence: 99%

Mesenchymal Stromal Cells and Toll-Like Receptor Priming: A Critical Review

et al. 2017

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“…Szabo et al showed that mouse BM-MSC exhibit differences between the clones in their ability to inhibit T cell proliferation, but after MSC pretreatment with proinflammatory cytokines, these differences disappear [51]. Fuenzalida et al demonstrated that pretreatment with a TLR3 ligand (poly I:C) enhances UC-MSC immunosuppressive capacity [52]. Unlike these studies, we observed that the variability is maintained after pretreatment with IFN- γ and that this proinflammatory stimulus does not seem to potentiate the inhibitory capacity of WJ-MSC upon T cells.…”

Section: Discussionmentioning

confidence: 99%

Intrinsic Variability Present in Wharton’s Jelly Mesenchymal Stem Cells and T Cell Responses May Impact Cell Therapy

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Sardinha

Piccinato

et al. 2017

Stem Cells International

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Wharton's jelly mesenchymal stem cells (WJ-MSC) exhibit immunomodulatory effects on T cell response. WJ-MSC are easy to collect, process, and proliferate rapidly in culture, but information on the variability of individual cell samples impacting upon in vitro expansion, immunomodulatory potential, and aging processes is still lacking. We propose to evaluate the immunomodulatory cytokine profile and capacity to inhibit T cell proliferation of WJ-MSC progressing to replicative senescence in order to analyze if expected responses are affected. Our results show that the gene expression of immunomodulatory molecules varied among samples with no specific pattern present. In coculture, all WJ-MSC were capable of inhibiting mitogen-activated CD3+ T cell proliferation, although to different degrees, and each PBMC responded with a different level of inhibition. Thus, we suggest that each WJ-MSC displays unique behavior, differing in patterns of cytokine mRNA expression and immunomodulatory capacity. We believe that variability between samples may play a role in the effectiveness of WJ-MSC employed therapeutically.

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“…42 Three studies recently set out that preconditioning MSCs with polyinosinic-polycytidylic acid (poly(I:C)), a ligand of TLR3, could enhance the therapeutic effects in experimental colitis. [43][44][45] In these studies, the investigators described two viewpoints: (a) TLR3-activated Notch-1 signalling regulated the immune suppression of MSCs through the production of PGE2. PGE2 was produced by MSCs in response to poly(I:C), which promoted the differentiation of Tregs and increased the production of IL-10.…”

Section: Pretreatment Enhances the Function Of Mscsmentioning

confidence: 99%

“…44 (b) Poly(I:C) preconditioning of MSCs increased the expression of indoleamine 2,3-dioxygenase (IDO), a treatment-related immunosuppressive factor. 43,45 Mancheño-Corvo et al 46 demonstrated that co-culture of prestimulated T lymphocytes with AD-MSCs impaired the ability of AD-MSCs to inhibit proliferation. However, the researchers could pre-activate AD-MSCs with IFN-γ or Poly I:C to restore their capacity to inhibit T lymphocyte proliferation.…”

Section: Pretreatment Enhances the Function Of Mscsmentioning

confidence: 99%

“…We just need to incubate MSCs with poly(I:C) for 1 or 24 hours (the pretreatment time is not uniform in reported studies) and then wash the cells in growth medium without poly(I:C). [43][44][45]49 Therefore, we believe that this may become a novel and acceptable method to improve the efficacy of MSCs in the treatment of IBD in the future.…”

Section: Pretreatment Enhances the Function Of Mscsmentioning

confidence: 99%

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Potential methods for improving the efficacy of mesenchymal stem cells in the treatment of inflammatory bowel diseases

et al. 2020

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Inflammatory bowel diseases (IBD) are a group of chronic recurrent gastrointestinal inflammatory diseases, including ulcerative colitis (UC), Crohn's disease (CD) and IBD unclassified. The pathogenesis may be related to the mucosal immune dysfunction in genetically susceptible hosts affected by environmental factors. Current therapeutic agents mainly include aminosalicylates, corticosteroids, immunosuppressive drugs and novel biological agents. The purpose of treatment is to suppress inflammation and prevent irreversible structural damage. However, long‐term application of these drugs may lead to multiple adverse effects and is not always effective. Mesenchymal stem cells (MSCs) are multipotent progenitors with low immunogenicity, which can be obtained and expanded easily. They play an important role in regulating immune responses and repairing damaged tissues in vivo. Therefore, MSCs are considered to be a promising option for the treatment of IBD. Nonetheless, there are many factors that can reduce the efficacy of MSCs, such as gradual deterioration of functional stem cells with age, low recruitment and persistence in vivo and different routes of administration. In recent years, researchers have been able to improve the efficacy of MSCs by pretreatment, genetic modification or co‐application with other substances, as well as using different tissue‐derived cells, administration methods or doses. This article reviews these methods to provide references for more effective application of MSCs in the treatment of IBD in the future.

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Toll-like receptor 3 pre-conditioning increases the therapeutic efficacy of umbilical cord mesenchymal stromal cells in a dextran sulfate sodium–induced colitis model

Cited by 45 publications

References 46 publications

Mesenchymal Stromal Cells and Toll-Like Receptor Priming: A Critical Review

Mesenchymal Stromal Cells and Toll-Like Receptor Priming: A Critical Review

Intrinsic Variability Present in Wharton’s Jelly Mesenchymal Stem Cells and T Cell Responses May Impact Cell Therapy

Potential methods for improving the efficacy of mesenchymal stem cells in the treatment of inflammatory bowel diseases

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