Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2–dependent regulatory dendritic cell population

Blood ◽  
2009 ◽  
Vol 113 (1) ◽  
pp. 46-57 ◽  
Author(s):  
Bin Zhang ◽  
Rui Liu ◽  
Dan Shi ◽  
Xingxia Liu ◽  
Yuan Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
Immune Cells ◽  
Cell Contact ◽  
Multilineage Differentiation ◽  
Immunomodulatory Effects ◽  
Cd11b Expression ◽  
Dendritic Cell Population

Abstract Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence the destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40 while increasing CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2–dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.

scholarly journals The Role of Tumor-Associated Macrophages in Leukemia

2019 ◽  
Vol 143 (2) ◽  
pp. 112-117 ◽  
Author(s):  
Yueyang Li ◽  
M. James You ◽  
Yaling Yang ◽  
Dongzhi Hu ◽  
Chen Tian
Keyword(s):  
Stem Cells ◽  
Innate Immunity ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Leukemia Cell ◽  
Tumor Associated Macrophages ◽  
Intrinsic Factors ◽  
Different Types ◽  
Tumor Growth And Metastasis

In addition to intrinsic factors, leukemia cell growth is influenced by the surrounding nonhematopoietic cells in the leukemic microenvironment, including fibroblasts, mesenchymal stem cells, vascular cells, and various immune cells. Despite the fact that macrophages are an important component of human innate immunity, tumor-associated macrophages (TAMs) have long been considered as an accomplice promoting tumor growth and metastasis. TAMs are activated by an abnormal malignant microenvironment, polarizing into a specific phenotype and participating in tumor progression. TAMs that exist in the microenvironment of different types of leukemia are called leukemia-associated macrophages (LAMs), which are reported to be associated with the progression of leukemia. This review describes the role of LAMs in different leukemia subtypes.

Inhibition of T Lymphocyte (TL) Proliferation by Mesenchymal Stem Cells (MSCs): Role of Cell Contact between MSCs and TL, Role of MSCs Dose Effect, and Role of Soluble Factors and Adhesion Molecules Expressed by MSCs.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4251-4251
Author(s):  
Aisha Nasef ◽  
Alain Chapel ◽  
Morad Benshidom ◽  
Yizhuo Zang ◽  
Christelle Mazurier ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Adhesion Molecules ◽  
T Lymphocyte ◽  
Dose Effect ◽  
Cell Contact ◽  
Rt Pcr ◽  
Soluble Factors

Abstract Mesenchymal stem cells (MSCs) can inhibit T lymphocyte (TL) proliferation in mixed lymphocyte reaction (MLR) and are candidate to induce tolerance of allogeneic haematopoietic stem cell graft. Results of previous studies evaluating the role of cell contact between MSCs and TL are contradictory. Some soluble factors produced by MSCs have been shown to be involved in TL inhibition such as Transforming Growth Factor-b (TGF-b), Hepatocyte Growth Factor (HGF), and Indoleamine 2,3 dioxygenase (IDO). In this study inhibition of TL proliferation in MLR was evaluated in cultures with MSCs-TL contact and in cultures without MSCs-TL contact (transwell), at different concentration of MSCs (ratio MSCs/TL: 0.3, 0.1, 0.03, 0.01). Expression of mRNA encoding cytokines and adhesion molecules produced by MSCs were analysed by semi-quantitative RT-PCR. Inhibitory cytokines studied were IDO, HLA-G, LIF, IL-10, TGF-b and HGF; adhesion molecules studied were VCAM and LFA3. Results of MSCs dose effect. In MLR with MSCs-TL contact, inhibition of proliferative index was related to the dose of MSCs. The percentage of inhibition was 74%, 60%, 48%, and 28% at ratio 0.3, 0.1, 0.03 and 0.01 respectively (p<0.05). In MLR without MSCs-TL contact, no dose effect was observed: the percentage of inhibition was 48%, 46% and 46% at ratio 0.3, 0.1 and 0.03 respectively; no inhibition was observed at ratio 0.01. Results of comparison between inhibition with cell contact and without cell contact. At ratio 0.3 the percentage of inhibition was 74% with cell contact and 48% without cell contact (p<0.05), at ration 0.1 the percentage of inhibition was 60% and 46% respectively (p<0.05). These results confirmed that TL inhibition is mediated by soluble factors but is increased when MSCs and TL are in contact. Results of mRNA RT-PCR in MSCs showed an overexpression of IDO, HLA-G and LIF in cultures with cell contact and without cell contact. In cultures with cell contact an overexpression of IL10 and TGF-b was observed, but not in cultures without cell contact. Adhesion molecules VCAM and LFA3 were overexpressed in both types of cultures with and without cell contact. In conclusion although cell contact is not mandatory to inhibit T cell proliferation, inhibition is higher when TL and MSCs are in contact, concomitantly an overexpression of additional inhibitory molecules is observed.

scholarly journals Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiangling Li ◽  
Yanjun Guan ◽  
Chaochao Li ◽  
Tieyuan Zhang ◽  
Fanqi Meng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peripheral Nerve ◽  
Immune Cells ◽  
Peripheral Nerve Injuries ◽  
Local Inflammatory Response ◽  
Inflammatory Microenvironment ◽  
Free Treatment ◽  
Immunomodulatory Potential

AbstractVarious immune cells and cytokines are present in the aftermath of peripheral nerve injuries (PNI), and coordination of the local inflammatory response is of great significance for the recovery of PNI. Mesenchymal stem cells (MSCs) exhibit immunosuppressive and anti-inflammatory abilities which can accelerate tissue regeneration and attenuate inflammation, but the role of MSCs in the regulation of the local inflammatory microenvironment after PNI has not been widely studied. Here, we summarize the known interactions between MSCs, immune cells, and inflammatory cytokines following PNI with a focus on the immunosuppressive role of MSCs. We also discuss the immunomodulatory potential of MSC-derived extracellular vesicles as a new cell-free treatment for PNI.

Evaluation of Immunomodulatory Effects of Mesenchymal Stem Cells Soluble Factors on miR-155 and miR-23b Expression in Mice Dendritic Cells

2015 ◽  
Vol 44 (5) ◽  
pp. 427-437 ◽  
Author(s):  
Aida Karachi ◽  
Mehdi Fazeli ◽  
Mohammad Hossein Karimi ◽  
Bita Geramizadeh ◽  
Ali Moravej ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
Immunomodulatory Effects ◽  
Soluble Factors

scholarly journals Biological relevance of cell-in-cell in cancers

2019 ◽  
Vol 47 (2) ◽  
pp. 725-732 ◽  
Author(s):  
Hannah L. Mackay ◽  
Patricia A.J. Muller
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Genomic Instability ◽  
Immune Cells ◽  
Living Cell ◽  
Cancer Biology ◽  
Tumour Cells ◽  
Mutant P53 ◽  
The Past

Abstract Cell-in-cell (CIC) is a term used to describe the presence of one, usually living, cell inside another cell that is typically considered non-phagocytic. Examples of this include tumour cells inside tumour cells (homotypic), mesenchymal stem cells inside tumour cells (heterotypic) or immune cells inside tumour cells (heterotypic). CIC formation can occur in cell lines and in tissues and it has been most frequently observed during inflammation and in cancers. Over the past 10 years, many researchers have studied CIC structures and a few different models have been proposed through which they can be formed, including entosis, cannibalism and emperipolesis among others. Recently, our laboratory discovered a role for mutant p53 in facilitating the formation of CIC and promoting genomic instability. These data and research by many others have uncovered a variety of molecules involved in CIC formation and have started to give us an idea of why they are formed and how they could contribute to oncogenic processes. In this perspective, we summarise current literature and speculate on the role of CIC in cancer biology.

In Vitro and In Vivo Immunomodulatory Effects of Mesenchymal Stem Cells from Adipose Tissue.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3098-3098 ◽  
Author(s):  
Rosa M. Yañez ◽  
Maria L. Lamana ◽  
Javier Garcia-Castro ◽  
Manuel Ramirez ◽  
Juan A. Bueren
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Bone Marrow Cells ◽  
Control Group ◽  
Cell Contact ◽  
Immunomodulatory Effects

Abstract Previous studies have shown the immunomodulatory properties of bone marrow mesenchymal stem cells (BM-MSCs), opening the possibility of using these cells for the treatment of graft-versus-host disease (GVHD) in patients transplanted with allogeneic hematopoietic grafts. Additionally, Phase I studies in patients with Crohn’s disease suggested the efficacy of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) for the healing of Crohn’s fistulas. In the present study we have investigated in vitro and in vivo, the immunomodulatory effects of Ad-MSCs, compared to BM-MSCs. We observed that both BM-MSCs and Ad-MSCs were negative for CD34, CD45, CD14, CD31 and MHC class I expression, while positive for CD29, CD44, CD90 and CD105. When studying the immunomodulatory effects of these cells in vitro, we found that - as happened with BM-MSCs - Ad-MSCs did not induce proliferation of allogeneic lymphocytes and were not lysed by cytotoxic T cells or alloreactive natural killer cells, indicating that Ad-MSCs are non-immunogenic. Additionally, the presence of Ad-MSCs inhibited in a dose-dependent fashion, both the mixed lymphocyte reaction (MLR) and the T cell proliferation induced by mitogens. To determine whether cell-to-cell contact between Ad-MSCs and PBMNCs was required for immunosuppression, transwell experiments were conducted. Phytohaemagglutinin (PHA)-stimulated lymphocytes were cultured in the upper chamber of a transwell, while irradiated Ad-MSCs remained in the lower chamber. As observed with BM-MSCs, Ad-MSCs were also capable of suppressing the lymphocytes proliferation in this transwell assay. When conditioned medium from Ad-MSCs was added to the MLR, the immuno-suppressive effect persisted, although at a lower level than that observed in a cell-to-cell contact system. Next we studied whether our in vitro findings were of significance in an in vivo mouse model of haploidentical transplantation. In these experiments irradiated F1(C57Bl/Balbc) recipient mice received 1x107 bone marrow cells from C57Bl mice, together with 2x107 splenocytes from the donor, to induce GVHD. One cohort of recipient mice received additional i.v. infusions of 5x105 mouse Ad-MSCs, administered at periodic intervals for up to 28 days post-transplant. When compared to the control group, the severity of the GVHD was significantly reduced in mice receiving Ad-MSCs. Our results suggest that Ad-MSCs obtained from adipose tissue may constitute a new and readily available source of immunomodulatory cells for the prophylaxis and/or treatment of GVHD in patients transplanted with allogeneic grafts.

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