scholarly journals Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell Polarization

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Zhu Zhu ◽  
Chaonan Han ◽  
Shuli Xian ◽  
Feng Zhuang ◽  
Feng Ding ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Cell Infiltration ◽  
Inflammatory Factors ◽  
Anti Inflammatory

Purpose. Recent evidence has shown that CD4+ T helper (Th) cells are involved in renal inflammation and fibrosis. However, whether renal fibrosis can be alleviated by intervening in the polarization of CD4+ T cells remains unknown. Our research investigated the effects of intravenously administered placenta mesenchymal stromal cells (PMSCs) or treatment with extracellular EVs (EVs) derived from PMSCs (PMSC-EVs) on the polarization of CD4+ T cells in rats with unilateral ureteral obstruction (UUO). We further verified how PMSCs affect inflammatory factor secretion and the levels of regulatory T (Treg) and Th17 CD4+ T cells in vitro. Materials and Methods. We evaluated renal interstitial inflammation and fibrosis by pathological section staining, tested the polarization of CD4+ T cells (Th17 and Treg phenotypes) by flow cytometry (FCM) and immunohistochemistry, and detected the cytokines secreted by CD4+ T cells by enzyme-linked immunosorbent assay (ELISA). Results. Compared with that of control rats, the renal tissue of PMSC-treated rats exhibited lower renal Masson scores and more Foxp3+ cell infiltration, with a significantly decreased IL17A+CD4+ T cell/CD4+ T cell ratio and a significantly elevated anti-inflammatory cytokine (IL-10) level. When CD4+ T cells were cocultured with PMSCs, CD4+IL17A+ cell percentages were decreased in a UUO model after 7 days of coculture with PMSCs. The secretion of TGF-β and IL-10 was significantly increased (P<0.05), while the secretion of IFN-γ, IL-17, and IL-6 was significantly decreased (P<0.05) in the PMSC coculture group. Moreover, after treatment with PMSC-EVs, tubulointerstitial fibrosis was alleviated, and Foxp3+/IL-17+ cell infiltration was increased in the kidneys of UUO model animals on day 7. Conclusions. PMSCs can convert the inflammatory environment into an anti-inflammatory environment by affecting the polarization of CD4+ T cells and macrophages, inhibiting the inflammatory factors IFN-γ and IL-17, and upregulating the expression of the anti-inflammatory factors TGF-β and IL-10, ultimately leading to renal protection. Such functions may be mediated by the paracrine activity of PMSC-EVs.

scholarly journals Mesenchymal Stromal Cells Prevent Renal Fibrosis in a Rat Model of Unilateral Ureteral Obstruction by Suppressing the Renin-Angiotensin System via HuR

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0148542 ◽  
Author(s):  
Marilena Gregorini ◽  
Valeria Corradetti ◽  
Chiara Rocca ◽  
Eleonora Francesca Pattonieri ◽  
Teresa Valsania ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Rat Model ◽  
Stromal Cells ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Renin Angiotensin System ◽  
Unilateral Ureteral Obstruction ◽  
Angiotensin System ◽  
Renin Angiotensin

Fate alteration of bone marrow-derived macrophages ameliorates kidney fibrosis in murine model of unilateral ureteral obstruction

2018 ◽  
Vol 34 (10) ◽  
pp. 1657-1668 ◽  
Author(s):  
Ying Yang ◽  
Xiaojian Feng ◽  
Xinyan Liu ◽  
Ying Wang ◽  
Min Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Unilateral Ureteral Obstruction ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pathological Feature ◽  
Kidney Fibrosis ◽  
Anti Inflammatory

AbstractBackgroundRenal fibrosis is a key pathological feature and final common pathway leading to end-stage kidney failure in many chronic kidney diseases. Myofibroblast is the master player in renal fibrosis. However, myofibroblasts are heterogeneous. Recent studies show that bone marrow-derived macrophages transform into myofibroblasts by transforming growth factor (TGF)-β-induced macrophage–myofibroblast transition (MMT) in renal fibrosis.MethodsTGF-β signaling was redirected by inhibition of β-catenin/T-cell factor (TCF) to increase β-catenin/Foxo in bone marrow-derived macrophages. A kidney fibrosis model of unilateral ureteral obstruction was performed in EGFP bone marrow chimera mouse. MMT was examined by flow cytometry analysis of GFP+F4/80+α-SMA+ cells from unilateral ureteral obstruction (UUO) kidney, and by immunofluorescent staining of bone marrow-derived macrophages in vitro. Inflammatory and anti-inflammatory cytokines were analysis by enzyme-linked immunosorbent assay.ResultsInhibition of β-catenin/TCF by ICG-001 combined with TGF-β1 treatment increased β-catenin/Foxo1, reduced the MMT and inflammatory cytokine production by bone marrow-derived macrophages, and thereby, reduced kidney fibrosis in the UUO model.ConclusionsOur results demonstrate that diversion of β-catenin from TCF to Foxo1-mediated transcription not only inhibits the β-catenin/TCF-mediated fibrotic effect of TGF-β, but also enhances its anti-inflammatory action, allowing therapeutic use of TGF-β to reduce both inflammation and fibrosis at least partially by changing the fate of bone marrow-derived macrophages.

scholarly journals Human Bone Marrow Derived Mesenchymal Stromal Cells Enhance the Number and Function of Umbilical Cord Blood Peripheral Tregs during IL-2 Driven Ex Vivo Expansion

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1116-1116
Author(s):  
Jeong-Su Do ◽  
Alex Y. Huang ◽  
Daniel Zwick ◽  
Fei Zhong ◽  
David Askew ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Foxp3 Expression ◽  
Ex Vivo Expansion ◽  
Mitochondrial Transfer ◽  
And Function

Abstract Tumor growth factor β (TGF-β)-induced peripheral regulatory T cells (pTreg) are a promising therapeutic cell source that exhibit Foxp3 expression and suppressive functions similar to natural regulatory T cells. Nonetheless, their clinical potential is limited by the instability of Foxp3 expression and T cell exhaustion that occurs during ex vivo expansion. We postulated that mesenchymal stromal cells (MSCs) could enhance the number, function and Foxp3 expression stability of pTregs during IL-2 driven 21 day expansion due to their diverse immunomodulatory properties. In this study, we observed that use of a human bone marrow mesenchymal stromal cells (hBM-MSC) platform significantly enhanced the number of pTreg during IL-2 driven 21 day ex vivo expansion vs. standard suspension culture condition (MSC platform: 80.2 x 106 vs. IL2/media: 39.3 x 106, n=6; p<0.01). Also the number of pTreg expressing a naive phenotype (CD4+CD45RA+ and CD4+CD62L+ ) were significantly increased (CD45RA+; MSC platform: 74.4 ± 1.6 x 106 vs. IL2/media: 45.9 ± 2.9 x 106, n=6, p<0.001; CD62L+; MSC platform: 79.1 ± 1.3 x 106 vs. IL2/media: 54.5 ± 2.1 x 106, n=6, p<0.001), as well as stability of Foxp3 expression (IL-2/media: 88.2 ± 1.7% vs. MSC platform: 96.2 ± 1.1%, n=7; p<0.05). In addition, pTreg suppressive function was noted to be more potent during 21 day IL-2 driven ex vivo expansion compared to standard IL-2/media culture condition (MSC platform: 79% vs. media: 35% inhibition of T cell proliferation in 10:1 ratio, n=6; p<0.01). pTreg expanded over a hBM-MSC platform exhibited higher surface CD25, CTLA-4, and ICOS MFI expression (CD25; MSC platform: 1410 vs. Media: 774; p<0.001, CTLA-4; MSC platform: 1084 vs. Media: 318; p<0.001, ICOS; MSC platform: 4386 vs. Media: 2641, p<0.01, n=6). Notably, hBM-MSC enhancement of pTreg ex vivo expansion requires direct cell-cell contact, as Foxp3 expression in pTreg was not enhanced by hBM-MSC conditioned media (CM:73.4 ± 6.8% vs. MSC platform: 96.2 ± 1.0%, p<0.001; and IL2/media: 88.8 ± 1.6% vs. MSC platform: 96.2 ± 1.0%, p<0.01) nor in a trans-well culture experiments (Transwell: 83.4 ± 2.5% vs. IL2/media: 88.8 ± 1.6%; and Transwell: 83.4 ± 2.5% vs. MSC platform: 96.2 ± 1.0%, p<0.01). Importantly, optical sectioning microscopy and flow cytometry revealed that hBM-MSC supports Treg number and function via direct contact-dependent mitochondrial transfer (Figure 1A-B). Cytochalasin B treatment blocked mitochondrial transfer, suggesting that tunneling nanotubes (TNT) facilitate mitochondrial transfer from hBM-MSC to pTreg during IL-2 driven ex vivo expansion (Mock: 2208 ± 122.1 vs. Cyto B: 923.8 ± 89 MFI, n=6, p<0.0001). Moreover, the quantity of ATP (n=6; p<0.01) mitochondrial potential of pTreg (MSC platform: 9010 ± 224.5 vs. media: 7316 ± 122.7 MFI, n=6; p<0.01) were significantly enhanced in pTreg during IL-2 driven ex vivo expansion over a hBM-MSC platform. Taken together, hBM-MSC significantly improves the number, maturation, and function of pTreg during 21 day IL-2 driven ex vivo expansion. We have identified one key mechanism of action of hBM-MSC underlying these favorable effects on pTreg during ex vivo expansion to be mitochondrial transfer via TNT. Notably, these studies identify a novel role of hBM-MSC to overcome current limitations in IL-2/media suspension culture conditions including T cell senescence, and loss of Foxp3 expression. Disclosures No relevant conflicts of interest to declare.

scholarly journals Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Yury Rubtsov ◽  
Кirill Goryunov ◽  
Аndrey Romanov ◽  
Yulia Suzdaltseva ◽  
George Sharonov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
T Cell Activation ◽  
Stromal Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Mixed Cultures ◽  
Activated T Cells

Mesenchymal stromal cells (MSC) control excessive inflammation and create a microenvironment for tissue repair protecting from chronic inflammation and tissue fibrosis. We examined the molecular mechanisms of MSC immunomodulatory function in mixed cultures of human adipose-derived MSC with lymphocytes. Our data show that MSC promote unstimulated lymphocyte survival potentially by an increase in antigen presentation. Under inflammatory conditions, mimicked by stimulation of TCR in lymphocytes, MSC suppress activation and proliferation of stimulated T cells. Immunosuppression is accompanied by downregulation of IL-2Rαthat negatively affects the survival of activated T cells. MSC upregulate transcription of indolamine-2,3-dioxygenase (IDO) and inducible NO synthase (iNOS), which generate products negatively affecting T cell function. Both MSC and lymphocytes dramatically increase the surface ICAM-1 level in mixed cultures. Antibody-mediated blockage of surface ICAM-1 partially releases MSC-mediated immune suppression in vitro. Our data suggest that MSC have cell-intrinsic molecular programs depending on the inflammatory microenvironment. We speculate that MSC sense soluble factors and respond by surface ICAM-1 upregulation. ICAM-1 is involved in the control of T cell activation leading to immunosuppression or modest stimulation depending on the T cell status. Immunomodulation by MSC ranging from support of naive T cell survival to immunosuppression of activated T cells may affect the tissue microenvironment protecting from aberrant regeneration.

scholarly journals Mesenchymal Stromal Cells from Osteoarthritic Synovium Are a Distinct Population Compared to Their Bone-Marrow Counterparts regarding Surface Marker Distribution and Immunomodulation of Allogeneic CD4+ T-Cell Cultures

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Sebastien Hagmann ◽  
Claudia Rimmele ◽  
Florin Bucur ◽  
Thomas Dreher ◽  
Felix Zeifang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cd4 T Cells ◽  
Surface Marker ◽  
Cd4 T Cell ◽  
T Cell Proliferation

Introduction. The participation of an inflammatory joint milieu has been described in osteoarthritis (OA) pathogenesis. Mesenchymal stromal cells (MSCs) play an important role in modulating inflammatory processes. Based on previous studies in an allogeneic T-cell coculture model, we aimed at further determining the role of synovial MSCs in OA pathogenesis.Methods. Bone-marrow (BM) and synovial membrane (SM) MSCs from hip joints of late stage OA patients and CD4+ T-cells from healthy donors were analysed regarding surface marker expression before and after coculture. Proliferation upon CD3/CD28 stimulation and cytokine analyses were compared between MSCs.Results. SM-MSCs differed from BM-MSCs in several surface markers and their osteogenic differentiation potential. Cocultures of both MSCs with CD4+ T-cells resulted in recruitment of CD45RA+ FoxP3+ regulatory T-cells. Upon stimulation, only SM-MSCs suppressed CD4+ T-cell proliferation, while both SM-MSCs and BM-MSCs modified cytokine profiles through suppressing IL-2 and TNF-αas well as increasing IL-6 secretion.Conclusions. Synovial MSCs from OA joints are a unique fraction that can be distinguished from their bone-marrow derived counterparts. Their unique ability to suppress CD3/CD28 induced CD4+ T-cell proliferation makes them a potential target for future therapeutic approaches.

scholarly journals Extracellular Vesicles isolated from Mesenchymal Stromal Cells Modulate CD4+ T Lymphocytes Toward a Regulatory Profile

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1059 ◽  
Author(s):  
Flavia Franco da Cunha ◽  
Vinicius Andrade-Oliveira ◽  
Danilo Candido de Almeida ◽  
Tamiris Borges da Silva ◽  
Cristiane Naffah de Souza Breda ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Confocal Microscopy ◽  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Target Genes ◽  
T Cell Response ◽  
Activated T Cells

Mesenchymal stromal cells (MSCs) can generate immunological tolerance due to their regulatory activity in many immune cells. Extracellular vesicles (EVs) release is a pivotal mechanism by which MSCs exert their actions. In this study, we evaluate whether mesenchymal stromal cell extracellular vesicles (MSC-EVs) can modulate T cell response. MSCs were expanded and EVs were obtained by differential ultracentrifugation of the supernatant. The incorporation of MSC-EVs by T cells was detected by confocal microscopy. Expression of surface markers was detected by flow cytometry or CytoFLEX and cytokines were detected by RT-PCR, FACS and confocal microscopy and a miRNA PCR array was performed. We demonstrated that MSC-EVs were incorporated by lymphocytes in vitro and decreased T cell proliferation and Th1 differentiation. Interestingly, in Th1 polarization, MSC-EVs increased Foxp3 expression and generated a subpopulation of IFN-γ+/Foxp3+T cells with suppressive capacity. A differential expression profile of miRNAs in MSC-EVs-treated Th1 cells was seen, and also a modulation of one of their target genes, TGFbR2. MSC-EVs altered the metabolism of Th1-differentiated T cells, suggesting the involvement of the TGF-β pathway in this metabolic modulation. The addition of MSC-EVs in vivo, in an OVA immunization model, generated cells Foxp3+. Thus, our findings suggest that MSC-EVs are able to specifically modulate activated T cells at an alternative regulatory profile by miRNAs and metabolism shifting.

scholarly journals Human delta like 1-expressing human mesenchymal stromal cells promote human T cell development and antigen-specific response in humanized NOD/SCID/IL-2R$$\upgamma $$null (NSG) mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Do Hee Kwon ◽  
Jae Berm Park ◽  
Joo Sang Lee ◽  
Sung Joo Kim ◽  
Bongkum Choi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Response ◽  
T Cell Development ◽  
Cell Development ◽  
T Cell Response ◽  
Nsg Mice ◽  
Human T Cells

AbstractHuman delta-like 1 (hDlk1) is known to be able to regulate cell fate decisions during hematopoiesis. Mesenchymal stromal cells (MSCs) are known to exhibit potent immunomodulatory roles in a variety of diseases. Herein, we investigated in vivo functions of hDlk1-hMSCs and hDlk1+hMSCs in T cell development and T cell response to viral infection in humanized NOD/SCID/IL-2Rγnull (NSG) mice. Co-injection of hDlk1-hMSC with hCD34+ cord blood (CB) cells into the liver of NSG mice markedly suppressed the development of human T cells. In contrast, co-injection of hDlk1+hMSC with hCD34+ CB cells into the liver of NSG dramatically promoted the development of human T cells. Human T cells developed in humanized NSG mice represent markedly diverse, functionally active, TCR V$$\upbeta $$ β usages, and the restriction to human MHC molecules. Upon challenge with Epstein-Barr virus (EBV), EBV-specific hCD8+ T cells in humanized NSG mice were effectively mounted with phenotypically activated T cells presented as hCD45+hCD3+hCD8+hCD45RO+hHLA-DR+ T cells, suggesting that antigen-specific T cell response was induced in the humanized NSG mice. Taken together, our data suggest that the hDlk1-expressing MSCs can effectively promote the development of human T cells and immune response to exogenous antigen in humanized NSG mice. Thus, the humanized NSG model might have potential advantages for the development of therapeutics targeting infectious diseases in the future.

scholarly journals Allogenic Use of Human Placenta-Derived Stromal Cells as a Highly Active Subtype of Mesenchymal Stromal Cells for Cell-Based Therapies

2021 ◽  
Vol 22 (10) ◽  
pp. 5302
Author(s):  
Raphael Gorodetsky ◽  
Wilhelm K. Aicher
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Human Placenta ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Feasibility Studies ◽  
Hla Class I ◽  
Inflammatory Factors ◽  
Competent Cell ◽  
Wide Range ◽  
Anti Inflammatory

The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of rejection in allogeneic or xenogeneic applications in normal immunocompetent hosts. The main advantage of hPSCs-based therapies seems to lie in the secretion of a wide range of pro-regenerative and anti-inflammatory factors. This renders hPSCs as a very competent cell for therapy in humans or animal models. This review summarizes the therapeutic potential of allogeneic applications of f-hPSCs, with reference to their indirect pro-regenerative and anti-inflammatory effects and discusses clinical feasibility studies.

Mesenchymal Stromal Cells Promote a Sustained Increase of the CD69 Marker on Activated CD3+ Lymphocytes: Potential Immunomodulatory Role

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2417-2417
Author(s):  
Felipe Saldanha Araujo ◽  
Rodrigo Alexandre Panepucci ◽  
Kelen Cristina Farias ◽  
Amelia G Araujo ◽  
Maristela Delgado Orellana ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immune Modulation ◽  
Regulatory Function ◽  
Sustained Increase

Abstract Mesenchymal stromal cells (MSCs) exert an immune regulatory function and suppress T-cell proliferation in vitro and in vivo. One of the ways by which MSCs may modulate immune responses is by the induction of CD4+CD25+FOXP3+ regulatory T cells (Treg), which suppress alloreactivity in vitro and prevent or attenuate GVHD in animal models. TGF-b (TGFB1 gene), one of the factors secreted by MSC, is known to induce the expression of FOXP3 and to drive the generation of Tregs from CD4+CD25− T cells. T cell activation is characterized by the expression of many surface molecules, and CD69 is one of the earliest markers, transiently expressed following activation. CD69 is selectively expressed at sites of chronic inflammation and recent in vivo and in vitro results indicate that this receptor may modulate the inflammatory response, by inducing TGF-b production. Despite the importance of secreted factors, cell to cell contacts promote increased lymphocyte immune modulation. Interestingly, TGF-b is known to induce the expression of b-IG-H3 (TGFBI gene), a secreted extracellular matrix adaptor protein, whose expression is higher on hematopoietic stem cells adherent to MSC. Given the potential role of CD69 as a regulatory molecule, we explored the effects of MSC on the expression of CD69, TGFB1, FOXP3 and TGFBI on co-cultured T-cells. Peripheral blood mononuclear cells (PBMC) from 6 individuals were co-activated by anti-CD3/CD28 beads and cultured either in the presence or in the absence of MSC (5:1) adhered to the bottom of culture wells. IL2 (20U/ml) was added in the 3rd day for full activation. Cultured PBMC were collected 1, 3 and 5 days after activation. Percentage of CD69+ cells and proliferation of activated lymphocytes (cell division tracking by CFSE) were evaluated by flow cytometry on gated CD3+ lymphocytes. Transcripts levels of TGFB1, TGFBI, FOXP3 and IL10 were determined by real time PCR and normalized using ACTB as an endogenous control. Relative expression levels were calculated in comparison with activated PBMC cultivated alone at the 5th day. Proliferation of lymphocytes co-cultured with MSC was significantly inhibited. As expected, activation of lymphocytes cultured alone was evidenced by the expression of CD69 in 5% of cells in the first day (mean percentage), followed by a decrease in the subsequent days (4% and 3%, respectively). Interestingly, lymphocytes co-cultured with MSC displayed a completely different pattern, with a similar initial activation (7%) which was followed by significant increase in the 3rd day (16%), maintained in the 5th day (14%). Furthermore, TGFBI and IL10 were both expressed at significantly higher levels on PBMC co-cultured with MSC, compared to PBMC alone, in all days evaluated. In addition, their transcript levels decreased faster on PBMC cultured alone. In the other hand, TGFB1 and FOXP3 levels in PBMC cultured alone or in the presence of MSC were similarly higher in the 1st day, but decreased till the 5th day, when their levels were slightly, but significantly higher on PBMC co-cultured with MSC, compared to PBMC cultured alone. We demonstrate for the first time that co-culture with MSC causes a sustained increase of the CD69 marker on CD3+ lymphocytes, which is accompanied by increased levels of TGFB1, TGFBI, FOXP3 and IL10 on total PBMC. Our results are in line with the proposed immunoregulatory role of CD69. In addition, higher TGFBI levels on PBMC may increase lymphocyte adherence to MSC, thus favoring immune modulation. This work was supported by FINEP, CNPq and FAPESP.

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