How mesenchymal stem cells interact with tissue immune responses

Shi, Yufang; Su, Juanjuan; Roberts, Arthur I.; Shou, Peishun; Rabson, Arnold B.; Ren, Guosheng

doi:10.1016/j.it.2011.11.004

Cited by 525 publications

(431 citation statements)

References 99 publications

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“…in the presence of low levels of pro-inflammatory cytokines such as IFN-g and TNF-a) can promote immune responses and that this involves the production of chemokines that recruit lymphocytes to sites of inflammation but insufficient levels of either NO (for murine MSCs) or IDO (for human MSCs) to inhibit T cell proliferation. Moreover, murine MSCs in which iNOS has been genetically ablated or pharmacologically inhibited have been shown to strongly enhance T cell proliferation (25,30,40,41). Further optimization of cytokine combinations and/or concentrations may be necessary to enhance therapeutic effects of syn-MSCs in this model.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy Promotes Corneal Allograft Survival in Rats by Local and Systemic Immunomodulation

Treacy

O’Flynn

Ryan

et al. 2014

American Journal of Transplantation

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y These authors contributed equally to this work.Mesenchymal stem cells (MSCs) are being investigated extensively due to their ability to dampen immune responses. Here, we tested the ability of MSCs from three distinct sources to prolong rat corneal allograft survival. A fully allogeneic rat cornea transplant model (DA to LEW) was used. Recipient rats received 1 Â 10 6 MSCs (syn [LEW], allo [DA] or third-party [Wistar Furth]) intravenously 7 days before transplantation and again on the day of transplantation (day 0). A high percentage of untreated and syn-MSC treated allografts were rejected (80% and 100%, respectively). Preactivation of syn-MSCs with interferon gamma also failed to prolong allograft survival. Conversely, corneal allograft survival was significantly prolonged in allo-MSC treated (90%) and third-party MSC treated (80%) allograft recipients. Flow cytometric analysis revealed less infiltrating natural killer T cells in corneas of both allo-and third-party MSC treated animals, coupled with a higher proportion of splenic CD4þFoxp3þ regulatory T cells, compared to controls. In the case of allo-and third-party MSCs, results from a delayed-type hypersensitivity assay clearly showed that hypo-responsiveness was specific for corneal donor-associated alloantigens. Thus, allo-and third-party MSC treatment prolongs corneal allograft survival by suppressing peripheral immune responses and promoting an intragraft immunoregulatory milieu.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy Promotes Corneal Allograft Survival in Rats by Local and Systemic Immunomodulation

Treacy

O’Flynn

Ryan

et al. 2014

American Journal of Transplantation

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“…Several studies have found that for MSC to suppress T cells, the MSC must first be activated by proinflammatory cytokines [18,19,23,60]. The major cytokine known to ''license'' MSC to become immune modulatory has been identified as IFN-g [36,60].…”

Section: Msc Activation By Ifn-c Required For Full Immune Suppressivementioning

confidence: 99%

“…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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“…Interaction and treatment of stem cells with inflammatory cytokines may also help enhance their therapeutic efficacy. This is well brought out in a mouse model with GvHD induced disease [26].…”

Section: Mscs In Tb and Other Infectionsmentioning

confidence: 86%