The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy

Hoogduijn, Martin J.; Popp, Felix; Verbeek, Richard; Masoodi, Mojgan; Nicolaou, Anna; Baan, Carla C.; Dahlke, Marc H.

doi:10.1016/j.intimp.2010.06.019

Cited by 217 publications

(176 citation statements)

References 48 publications

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“…Numerous studies have investigated the underlying mechanisms that drive the immune modulatory properties of both human and mouse MSC [16,[18][19][20]. In human MSC, the reported pathways of immune suppression by MSC include the indoleamine 2,3-deoxygenase (IDO) [21,22], cyclooxygenase [23][24][25], TGF-b [26], soluble IL-1Ra [27,28], soluble MHC [29,30], and the PD-L1 pathways [31,32].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

ChowLyndah

JohnsonValerie

CoyJonathan

et al. 2017

Stem Cells and Development

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Mesenchymal stem cells (MSCs) from rodents and humans have been shown to suppress T cells by distinct primary pathways, with nitric oxide (NO)-dependent pathways dominating in rodents and indoleamine 2,3-deoxygenase (IDO)-dependent pathways dominating in humans. However, the immune suppressive pathways utilized by canine MSC have not been thoroughly studied, nor have bone marrow-derived MSC (BM-MSC) and adipose-derived MSC (Ad-MSC) been directly compared for their immune modulatory potency or pathway utilization. Therefore, canine BM-MSC and Ad-MSC were generated in vitro and their potency in suppressing T cell proliferation and cytokine production was compared, and differential gene expression. Mechanisms of T cells suppression were also investigated for both MSC types. We found that BM-MSC and Ad-MSC were roughly equivalent in terms of their ability to suppress T cell activation. However, the two MSC types used both shared and distinct biochemical pathways to suppress T cell activation. Ad-MSC utilized TGF-b signaling pathways and adenosine signaling to suppress T cell activation, whereas BM-MSC used cyclooxygenase, TGF-b and adenosine signaling pathways to suppress T cell activation. These results indicate that canine MSC are distinct from human and rodent MSC terms of their immune suppressive pathways, relying primarily on cyclooxygenase and TGF-b pathways for T cell suppression, rather than on NO or IDO-mediated pathways.

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Section: Introductionmentioning

confidence: 99%

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

ChowLyndah

JohnsonValerie

CoyJonathan

et al. 2017

Stem Cells and Development

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“…Mesenchymal stromal stem cells (MSCs) are one of the best characterized adult stem cells and have emerged as attractive candidates for cell therapies. They are 4 present in virtually all tissues and can be derived from umbilical cord blood, adipose tissue, or most commonly, bone marrow [7]. MSCs have a direct immunosuppressive effect, which has been exploited in clinical studies over the last decade to treat graft versus host disease and other immunologically mediated conditions including acute and chronic pulmonary disease [4].…”

Section: Mesenchymal Stem Cells: a Vehicle To Deliver Anticancer Thermentioning

confidence: 99%

Combined cell-gene therapy for lung cancer: rationale, challenges and prospects

Thakrar

Sage

Janes

2016

Expert Opinion on Biological Therapy

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Lung cancer causes more deaths worldwide than any other cancer with most patients presenting with incurable metastatic disease. Mesenchymal stem cell tumour tropism presents us with an interesting mechanism of delivering potent therapies locally to cancers. Genetic modification of MSCs enables continued delivery of selective anticancer treatments such as TRAIL. While this is an attractive therapeutic option, translating such a therapy into patients presents challenges both in manufacture and delineation of dose and dosing strategy. However, successful delivery of a combined cell-gene therapy in lung cancer may offer promise to thousands of individuals largely resigned to poorly effective palliative treatments.

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“…For example, the beneficial activities of mesenchymal SCs are mediated by the secretion of pro-regenerative and antiinflammatory growth factors in cardiac repair 97 or graftversus-host disease. 98 miRNAs may be shuttled between cells packaged in small membrane-bound extracellular vesicles (EVs) (eg, exosomes, shedding vesicles, apoptotic bodies) that can then amend gene expression of their target cells. 99 Thus, as a natural extension we hypothesize that cells could be used to deliver miRNAs to promote tissue regeneration.…”

Section: Mirna In Cell-based Therapiesmentioning

confidence: 99%