Transplantation of Human Bone Marrow Mesenchymal Stem Cell Ameliorates the Autoimmune Pathogenesis in MRL/lpr Mice

Zhou, Kangxing; Zhang, Huayong; Ouyang, Jingping; Feng, Xuebing; Yao, Genhong; Hou, Yayi; Sun, Lingyun

doi:10.1038/cmi.2008.52

Cited by 175 publications

(152 citation statements)

References 15 publications

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“…The Journal of Immunology 5891 decrease in IL-2 production by 5-d cultures with MSCs is consistent with other studies that reported on the inhibitory effects of MSCs on T cell proliferation (36,41,42). The mechanisms of suppression, especially cytokine involvement, are critical to further understand the findings in our study.…”

Section: Discussionsupporting

confidence: 81%

Mesenchymal Stem Cells Protect Breast Cancer Cells through Regulatory T Cells: Role of Mesenchymal Stem Cell-Derived TGF-β

Patel

Meyer

Greco

et al. 2010

The Journal of Immunology

356

291

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Mesenchymal stem cells (MSCs) have been shown to support breast cancer growth. Because MSCs also increase the frequency of regulatory T cells (Tregs), this study tested the hypothesis that human MSCs, via Tregs, protect breast cancer cells (BCCs) from immune clearance MSCs suppressed the proliferation of PBMCs when the latter were exposed to gamma-irradiated BCCs. Similarly, MSCs showed significant inhibition of PBMC migration toward BCCs and a corresponding decrease in CXCL12. MSCs also inhibited NK cell and CTL functions, which correlated with reduced numbers of CD8+ and CD56+ cells compared with parallel cultures without MSCs. The reduced NK and CTL activities correlated with a decrease in intracellular and secreted granzyme B. To explain these immunosuppressive findings, we compared Treg levels after coculture with MSCs and found an ∼2-fold increase in Tregs, with associated decreases in antitumor Th1 cytokines and increases in Th2 cytokines. MSC-derived TGF-β1 was largely responsible for the increase in Tregs based on knockdown studies. In the presence of Treg depletion, PBMC proliferation and effector functions were partially restored. Together, these studies show an MSC-mediated increase in Tregs in cocultures of PBMCs and BCCs. The results could be explained, in part, by the increase in Th2-type cytokines and MSC-generated TGF-β1. These findings demonstrate immune protection by MSCs to BCCs. The reduction in immune cell proliferation and recruitment mediated by MSCs has implications for treatment of breast cancer with chemotherapy.

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Section: Discussionsupporting

confidence: 81%

Mesenchymal Stem Cells Protect Breast Cancer Cells through Regulatory T Cells: Role of Mesenchymal Stem Cell-Derived TGF-β

Patel

Meyer

Greco

et al. 2010

The Journal of Immunology

356

291

View full text Add to dashboard Cite

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“…For example, MSC derived from adipose tissues or bone marrow have been used to treat experimental allergic encephalitis, inflammatory bowel disease, immune-mediated arthritis, airway inflammation, and graft-versus-host disease in rodent models [1,[9][10][11][12]. In addition, human MSC have been administered to rodent models of inflammatory diseases [13][14][15][16][17]. Thus, it is apparent that the immune modulatory properties of MSC can be utilized therapeutically in a number of different diseases settings.…”

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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“…[5][6][7] To date, bone marrow-derived MSCs (BM-MSCs) are among the most commonly used MSCs in pre-clinical research for the treatment of rheumatoid arthritis (RA) and other autoimmune diseases. [8][9][10] However, there are some limitations associated with BM-MSCs in clinical applications, including the technical difficulty in acquiring sufficient numbers of cells for therapy. 11 Recently, olfactory ecto-mesenchymal stem cells (OE-MSCs), a new type of resident stem cell in the olfactory lamina propria, have been characterized.…”

Section: Introductionmentioning

confidence: 99%

Olfactory ecto-mesenchymal stem cells possess immunoregulatory function and suppress autoimmune arthritis

et al. 2015

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Transplantation of Human Bone Marrow Mesenchymal Stem Cell Ameliorates the Autoimmune Pathogenesis in MRL/lpr Mice

Cited by 175 publications

References 15 publications

Mesenchymal Stem Cells Protect Breast Cancer Cells through Regulatory T Cells: Role of Mesenchymal Stem Cell-Derived TGF-β

Mesenchymal Stem Cells Protect Breast Cancer Cells through Regulatory T Cells: Role of Mesenchymal Stem Cell-Derived TGF-β

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

Olfactory ecto-mesenchymal stem cells possess immunoregulatory function and suppress autoimmune arthritis

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