scholarly journals Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Guoping Zheng ◽  
Menghua Ge ◽  
Guanguan Qiu ◽  
Qiang Shu ◽  
Jianguo Xu
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Spinal Cord Injuries ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Cell Contact ◽  
Direct Cell ◽  
Almost All ◽  
Preclinical And Clinical Studies ◽  
Antigen Presenting

Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-αstimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models.

scholarly journals The Origins and Generation of Cancer-Associated Mesenchymal Stromal Cells: An Innovative Therapeutic Target for Solid Tumors

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Li ◽  
Jin Yang ◽  
Ping Zheng ◽  
Haining Li ◽  
Shaolin Zhao
Keyword(s):  
Cancer Therapy ◽  
Tumor Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Chemotherapy Resistance ◽  
Tissue Type ◽  
Cell Contact ◽  
Local Resident ◽  
Anti Cancer ◽  
Direct Cell

Cancer-associated mesenchymal stromal cells (CA-MSCs) have been isolated from various types of tumors and are characterized by their vigorous pro-tumorigenic functions. However, very little is known about the origins and generating process of CA-MSCs, which may facilitate the identification of biomarkers for diagnosis or innovative targets for anti-cancer therapy to restrain the tumor growth, spread and chemotherapy resistance. Current evidences have indicated that both distally recruited and local resident MSCs are the primary origins of CA-MSCs. In a tissue type-dependent mode, tumor cells together with the TME components prompt the malignant transition of tumor “naïve” MSCs into CA-MSCs in a direct cell-to-cell contact, paracrine or exosome-mediated manner. In this review, we discuss the transition of phenotypes and functions of naïve MSCs into CA-MSCs influenced by tumor cells or non-tumor cells in the TME. The key areas remaining poorly understood are also highlighted and concluded herein.

scholarly journals Management of Fibrosis: The Mesenchymal Stromal Cells Breakthrough

2014 ◽  
Vol 2014 ◽  
pp. 1-26 ◽  
Author(s):  
Benoît Usunier ◽  
Marc Benderitter ◽  
Radia Tamarat ◽  
Alain Chapel
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Inflammatory Diseases ◽  
Ability To Act ◽  
Slow Progression ◽  
Extracellular Matrix Components ◽  
Experimental Therapies ◽  
Abnormal Accumulation ◽  
Preclinical And Clinical Studies

Fibrosis is the endpoint of many chronic inflammatory diseases and is defined by an abnormal accumulation of extracellular matrix components. Despite its slow progression, it leads to organ malfunction. Fibrosis can affect almost any tissue. Due to its high frequency, in particular in the heart, lungs, liver, and kidneys, many studies have been conducted to find satisfactory treatments. Despite these efforts, current fibrosis management therapies either are insufficiently effective or induce severe adverse effects. In the light of these facts, innovative experimental therapies are being investigated. Among these, cell therapy is regarded as one of the best candidates. In particular, mesenchymal stromal cells (MSCs) have great potential in the treatment of inflammatory diseases. The value of their immunomodulatory effects and their ability to act on profibrotic factors such as oxidative stress, hypoxia, and the transforming growth factor-β1 pathway has already been highlighted in preclinical and clinical studies. Furthermore, their propensity to act depending on the microenvironment surrounding them enhances their curative properties. In this paper, we review a large range of studies addressing the use of MSCs in the treatment of fibrotic diseases. The results reported here suggest that MSCs have antifibrotic potential for several organs.

871 In vitro immunoregulatory effect from cervical cancer derived mesenchymal stromal cells over molecules expression in monocyte derived macrophage polarization

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A923-A923
Author(s):  
Víctor Cortés-Morales ◽  
Juan Montesinos ◽  
Luis Chávez-Sánchez ◽  
Sandra Espíndola-Garibay ◽  
Alberto Monroy-García ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Macrophage Polarization ◽  
Induction Medium ◽  
M2 Macrophage ◽  
List Type ◽  
M2 Phenotype

BackgroundMacrophages are immunological cells that sense microenvironmental signals that may result in the polarized expression of either proinflammatory (M1) or anti-inflammatory (M2) phenotype.1 Macrophages M2 are present in tumoral microenvironment and their presence in patients with cervical cancer (CeCa) is related with less survival.2Mesenchymal Stromal Cells (MSCs) are also present in tumor microenvironment of cervical cancer (CeCa-MSC), which have shown immunoregulatory effects over CD8 T cells, decreasing their cytotoxic effect against tumoral cells.3 Interestingly, MSCs from bone marrow (BM-MSC) decrease M1 and increase M2 macrophage polarization in an in vitro coculture system.4 Macrophages and MSCs are present in microenvironment of cervical cancer, however it is unknown if MSCs play a role in macrophage polarization. In the present study, we have evaluated the immunoregulatory capacity of CeCa-MSCs to induce macrophage polarization.MethodsCD14 monocytes were isolated from peripheral blood and cultivated in the absence or presence of MSCs from BM, normal cervix (NCx) and CeCa. Two culture conditions were included, in the presence of induction medium to favors M1 (GM-CSF, LPS and IFNg) or M2 (M-CSF, IL-4 and IL-13) macrophage polarization. M1 (HLA-DR, CD80, CD86 and IFNg) or M2 (CD14, CD163, CD206, IDO and IL-10) macrophage molecular markers were evaluated by flow cytometry. Finally, we evaluated concentration of IL-10 and TNFa in conditioned medium form all coculture conditions.ResultsWe observed that CeCa-MSCs and BM-MSCs in presence of M1 induction medium, decreased M1 macrophage markers (HLA-II, CD80, CD86 and IFNg), and increase the expression of CD14 (M2 macrophage marker). Interestingly, in presence of M2 induction medium, BM-MSCs and CaCe-MSCs but not CxN-MSC increased CD163, CD206, IDO and IL-10 (M2 macrophage markers). We observed a decreased concentration of TNFa in the supernatant medium from all cocultures with MSCs, but only in presence of CeCa-MSCs, increased IL-10 concentration was detected in such cocultures.ConclusionsIn contrast to NCx-MSCs, CeCa-MSCs similarly to BM-MSCs have in vitro capacity to decrease M1 and increase M2 macrophage phenotype.AcknowledgementsAcknowledgments The authors are indebted to gratefully acknowledge to CONACYT (Grant No. 272793) and IMSS (Grant no. 1731) for support to Juan J. Montesinos research.ReferencesMartinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 2014;6-13.Petrillo M, Zannoni GF, Martinelli E, et al. Polarization of tumor-associated macrophages toward M2 phenotype correlates with poor response to chemoradiation and reduced survival in patients with locally advanced cervical cancer. PLoS One 2015;10: e0136654.Montesinos JJ, Mora-García Mde L, et al. In vitro evidence of the presence of mesenchymal stromal cells in cervical cancer and their role in protecting cancer cells from cytotoxic T cell activity. Stem Cells Dev 2013;22:2508-2519.Vasandan AB, Jahnavi S, Shashank C. Human mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE 2-dependent mechanism. Sci Rep 2016;6:38308.

scholarly journals Perinatal Mesenchymal Stromal Cells and Their Possible Contribution to Fetal-Maternal Tolerance

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1401 ◽  
Author(s):  
Marta Magatti ◽  
Francesca Romana Stefani ◽  
Andrea Papait ◽  
Anna Cargnoni ◽  
Alice Masserdotti ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immune Cell ◽  
Immune Cell Subsets ◽  
New Perspective ◽  
Antigen Presenting ◽  
Open Question ◽  
Maternal Tolerance

During pregnancy, a successful coexistence between the mother and the semi-allogenic fetus occurs which requires a dynamic immune system to guarantee an efficient immune protection against possible infections and tolerance toward fetal antigens. The mechanism of fetal-maternal tolerance is still an open question. There is growing in vitro and in vivo evidence that mesenchymal stromal cells (MSC) which are present in perinatal tissues have a prominent role in generating a functional microenvironment critical to a successful pregnancy. This review highlights the immunomodulatory properties of perinatal MSC and their impact on the major immune cell subsets present in the uterus during pregnancy, such as natural killer cells, antigen-presenting cells (macrophages and dendritic cells), and T cells. Here, we discuss the current understanding and the possible contribution of perinatal MSC in the establishment of fetal-maternal tolerance, providing a new perspective on the physiology of gestation.

scholarly journals Adipose-derived Mesenchymal Stromal Cells Modulate Lipid Metabolism and Lipid Droplet Biogenesis via AKT/mTOR –PPARγ Signalling in Macrophages

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Luciana Souza-Moreira ◽  
Vinicius Cardoso Soares ◽  
Suelen da Silva Gomes Dias ◽  
Patricia T. Bozza
Keyword(s):  
Conditioned Medium ◽  
Lipid Droplet ◽  
Mesenchymal Stromal Cells ◽  
Tissue Regeneration ◽  
Stromal Cells ◽  
Lipid Droplets ◽  
Mtor Inhibitor ◽  
Inflammatory Diseases ◽  
Experimental Colitis ◽  
Arginase 1

AbstractMesenchymal stromal cells (MSCs) are a potential therapy for many chronic inflammatory diseases due to their regenerative, immunologic and anti-inflammatory properties. The two-way dialogue between MSCs and macrophages is crucial to tissue regeneration and repair. Previous research demonstrated that murine adipose-derived MSC conditioned medium (ASCcm) reprograms macrophages to an M2-like phenotype which protects from experimental colitis and sepsis. Here, our focus was to determine the molecular mechanism of lipid droplet biogenesis in macrophages re-educated using ASCcm. Adipose-derived MSC conditioned medium promotes phosphorylation of AKT/mTOR pathway proteins in macrophages. Furthermore, increased expression of PPARγ, lipid droplet biogenesis and PGE2 synthesis were observed in M2-like phenotype macrophages (high expression of arginase 1 and elevated IL-10). Treatment with mTOR inhibitor rapamycin or PPARγ inhibitor GW9662 suppressed lipid droplets and PGE2 secretion. However, these inhibitors had no effect on arginase-1 expression. Rapamycin, but not GW9662, inhibit IL-10 secretion. In conclusion, we demonstrate major effects of ASCcm to reprogram macrophage immunometabolism through mTOR and PPARγ dependent and independent pathways.

scholarly journals Dose and duration of interferon γ pre-licensing interact with donor characteristics to influence the expression and function of indoleamine-2,3-dioxygenase in mesenchymal stromal cells

2020 ◽  
Vol 17 (167) ◽  
pp. 20190815
Author(s):  
Devlin T. Boyt ◽  
Lauren K. Boland ◽  
Anthony J. Burand ◽  
Alex J. Brown ◽  
James A. Ankrum
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Interferon Γ ◽  
Relative Role ◽  
Peripheral Blood Mononuclear ◽  
High Performing ◽  
Indoleamine 2,3 Dioxygenase

Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon γ (IFNγ) exposure has been proposed as both a sentinel marker and key mediator of MSC immunomodulatory potency. Rather than wait for in vivo exposure to cytokines, MSCs can be pre-licensed during manufacturing to enhance IDO expression. In this study, we systematically examine the relative role that the dose of IFNγ, the duration of pre-licensing and the donor of origin play in dictating MSC production of functional IDO. We find that across three human MSC donors, MSCs increase their expression of IDO in response to both increased dose of IFNγ and duration of pre-licensing. However, with extended pre-licensing, the expression of IDO no longer predicts MSCs ability to suppress activated peripheral blood mononuclear cells. In addition, pre-licensing dose and duration are revealed to be minor modifiers of MSCs inherent potency, and thus cannot be manipulated to boost poor donors to the levels of high-performing donors. Thus, the dose and duration of pre-licensing should be tailored to optimize performance of specific donors and an emphasis on donor selection is needed to realize significant benefits of pre-licensing.

scholarly journals Mesenchymal Stromal Cells from Fetal and Maternal Placenta Possess Key Similarities and Differences: Potential Implications for Their Applications in Regenerative Medicine

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 127 ◽  
Author(s):  
Andrea Papait ◽  
Elsa Vertua ◽  
Marta Magatti ◽  
Sabrina Ceccariglia ◽  
Silvia De Munari ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immune Cell ◽  
Allogeneic Transplantation ◽  
Cell Polarization ◽  
T Regulatory Cell ◽  
T Lymphocyte Proliferation ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Antigen Presenting

Placenta-derived mesenchymal stromal cells (MSC) have attracted more attention for their immune modulatory properties and poor immunogenicity, which makes them suitable for allogeneic transplantation. Although MSC isolated from different areas of the placenta share several features, they also present significant biological differences, which might point to distinct clinical applications. Hence, we compared cells from full term placenta distinguishing them on the basis of their origin, either maternal or fetal. We used cells developed by Pluristem LTD: PLacenta expanded mesenchymal-like adherent stromal cells (PLX), maternal-derived cells (PLX-PAD), fetal-derived cells (PLX-R18), and amniotic membrane-derived MSC (hAMSC). We compared immune modulatory properties evaluating effects on T-lymphocyte proliferation, expression of cytotoxicity markers, T-helper and T-regulatory cell polarization, and monocyte differentiation toward antigen presenting cells (APC). Furthermore, we investigated cell immunogenicity. We show that MSCs and MSC-like cells from both fetal and maternal sources present immune modulatory properties versus lymphoid (T cells) and myeloid (APC) cells, whereby fetal-derived cells (PLX-R18 and hAMSC) have a stronger capacity to modulate immune cell proliferation and differentiation. Our results emphasize the importance of understanding the cell origin and characteristics in order to obtain a desired result, such as modulation of the inflammatory response that is critical in fostering regenerative processes.

scholarly journals Mesenchymal stromal cells release CXCL1/2/8 and induce chemoresistance and macrophage polarization

2018 ◽  
Author(s):  
Bettina Couderc ◽  
Augustin Le Naour ◽  
Mélissa Prat ◽  
Renaud Mevel ◽  
Benoit Thibault ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Strategy ◽  
Ex Vivo ◽  
Macrophage Polarization ◽  
Activated Macrophages ◽  
High Concentrations ◽  
Ovarian Tumor Cells

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells (CA-MSCs) are involved in tumor progression and chemoresistance. We determine the mechanisms by which a naïve MSC could become a CA-MSC and characterize CA-MSCs. Ovarian tumor cells (OTC) trigger the transformation of MSCs to CA-MSCs expressing different pro-tumoral, genes and secreting high amounts of CXCR1/2 ligands (CXCL1, CXCL2 and IL-8) implicated in the chemoresistance of cancer cells. CXCR1/2 ligands can also inhibit the immune response against OTC. Indeed, through their released factors, CA-MSCs can trigger the differentiation of monocytes to pro-tumoral M2 phenotype macrophages known to promote the tumor progression. When CXCR1/2 receptors are inhibited, these CA-MSC-activated macrophages lose their M2 functions and acquire an anti-tumoral phenotype. Both ex vivo and in vivo a CXCR1/2 inhibitor can sensitize OTC to carboplatin even in the presence of a pro-tumoral microenvironment. This inhibitor can circumvent the pro-tumoral effects of CA-MSCs. As high concentrations of CXCR1/2 ligands in blood from patients can be associated with chemoresistance, CXCR1/2 inhibition could be a potential therapeutic strategy to revert chemoresistance.

scholarly journals Immunoregulatory Properties of Apoptotic Human Amniontic Mesenchymal Stromal Cells

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5678-5678
Author(s):  
Ying Xu ◽  
Ya Gao ◽  
Yan chun Yang ◽  
Dongmao Zhu ◽  
Yintian Zhang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Natural Science ◽  
Guangdong Province ◽  
Morphological Features ◽  
Cell Contact ◽  
Tnf Α ◽  
Ifn Γ ◽  
Tgf Β1

Abstract Objective Mesenchymal stromal cells (MSCs) have been used in preventing and treating acute graft-versus-host disease (aGVHD), but the mechanism is not fully understood. Apoptotic bone marrow mesenchymal stromal cells (BMSCs) were showed could induce vivo recipient-mediated immunomodulation in mice GVHD model. We had demonstrated that, similar to BM-MSCs, human amniontic mesenchymal stromal cells (hAMSCs) exhibit potent immunosuppressive and anti-inflammatory activities but possess a higher proliferation activity and clearer stem cell properties in vitro. This study focuses on the immunoregulatory properties of apoptotic human amniontic mesenchymal stromal cells (apo-hAMSCs) in an inflammatory microenvironment. Methods hAMSCs from human amniotic membrane were cultured with tissue mass cell culture. The cell phenotype of the 3rd passage were detected by flow cytometry. Transwell co-culture experiments and cell-cell contact co-culture experiments were conducted, consisting of hAMSCs and peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA-PBMCs), as the positive control group. While other groups were PBMCs without PHA and hAMSCs(PBMCs+hAMSCs), PBMCs and PHA (PHA-PBMCs), hAMSCs and PBMCs. For apoptosis evalution, the morphological features of hAMSCs were recorded in different groups, and apo-hAMSCs were analyzed by flow cytometry at 24 hours. The production of Interferon-γ (IFN-γ), transforming growth factor-β1 (TGF-β1), prostaglandin E2 (PGE-2), soluble human leukocyte antigen G (sHLA-G), Tumor necrosis factor-α(TNF-α) and interleukin-17A (IL-17A) in the co-culture supernatant was detected using enzyme-linked immunosorbent assay (ELISA), and kynurenine were dectected by spectrophotometer. CD4+CD25+FOXP3+ regulatory T cells (Tregs) in PBMC were analyaed by flow cytometry. Result hAMSCs expressed CD105, CD73, CD90, while not CD19, CD34, CD45, CD11b, HLA-DR. In the group of hAMSCs and PHA-PBMCs, the number of hAMSCs reduced. The morphological features were that cells shrinked, turned round, separated from the bottle and suspended in supernatant. However, hAMSCs in the groups of hAMSCs+PBMCs and hAMSCs stayed the same. Apoptosis in hAMSCs cultivated with PHA-PBMCs via transwell or cell-cell contact experiment increased compared with the group of hAMSCs+PBMCs (P<0.05) and hAMSCs (P<0.05). In the two co-culture experments, the secretion level of PGE-2, TGF-β1, sHLA-G, and KYN significantly increased in hAMSCs with PHA-PBMCs compared with hAMSC (P<0.05) and hAMSCs with PBMCs (P<0.05). The level of IFN-γ and TNF-α decreased in hAMSCs with PHA-PBMCs compared with PBMCs with PHA (P<0.05). While the level of IL-17A was significantly increase in hAMSCs with PHA-PBMCs compared with hAMSCs (P<0.05), hAMSCs with PBMCs (P<0.05) and PHA-PBMCs (P>0.05). Evident difference of CD4+CD25+FOXP3+ Tregs was shown between hAMSCs with PHA-PBMCs and PHA-PBMCs (P<0.05). Conclusion Activated, but not resting, PBMCs induce extensive early apoptosis in hAMSCs. And apoptosis in hAMSCs need inflammatory microenvirenment. Apoptotic hAMSCs still have immunoregulatory effects in cytokines and immune cells. Funding This work was supported by Natural Science Foundation of China (81701243), Key Sci-Tech Research Projects of Guangdong Province (2014A02021102), Natural Science Foundation of Guangdong Province, China (2014A030310373), the Pearl River S&T Nova Program of Guangzhou (201710010047). Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document