scholarly journals Differential Effector Response of Amnion- and Adipose-Derived Mesenchymal Stem Cells to Inflammation; Implications for Intradiscal Therapy

2019 ◽  
Author(s):  
Ryan Borem ◽  
Allison Madeline ◽  
Mackenzie Bowman ◽  
Sanjitpal Gill ◽  
John Tokish ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Optimal Choice ◽  
Human Mscs ◽  
Tissue Destruction ◽  
Effector Functions ◽  
Anti Inflammatory ◽  
Factor Α ◽  
The Impact

ABSTRACTIntervertebral disc degeneration (IVDD) is a progressive condition marked by inflammation and tissue destruction. The effector functions of mesenchymal stem cells (MSCs) make them an attractive therapy for patients with IVDD. While several sources of MSCs exist, the optimal choice for use in the inflamed IVD remains a significant question. Adipose (AD)- and amnion (AM)-derived MSCs have several advantages compared to other sources, however, no study has directly compared the impact of IVDD inflammation on their effector functions. Human MSCs were cultured in media with or without supplementation of interleukin-1β and tumor necrosis factor-α at concentrations produced by IVDD cells. MSC proliferation and production of pro- and anti-inflammatory cytokines were quantified following 24- and 48-hours of culture. Additionally, the osteogenic and chondrogenic potential of AD- and AM-MSCs was characterized via histology and biochemical analysis following 28 days of culture. In inflammatory culture, AM-MSCs produced significantly more anti-inflammatory IL-10 (p=0.004) and larger chondrogenic pellets (p=0.04) with greater percent area staining positively for glycosaminoglycan (p<0.001) compared to AD-MSCs. Conversely, AD-MSCs proliferated more resulting in higher cell numbers (p=0.048) and produced higher concentrations of pro-inflammatory cytokines PGE2 (p=0.030) and IL-1β (p=0.010) compared to AM-MSCs. Additionally, AD-MSCs produced more mineralized matrix (p<0.001) compared to AM-MSCs. These findings begin to inform researchers and clinicians as to which MSC source may be optimal for different IVD therapies including those that may promote regeneration or fusion. Further study is warranted evaluating these cells in systems which recapitulate the nutrient- and oxygen-deprived environment of the degenerate IVD.

scholarly journals Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shengchao Zhang ◽  
Jiankai Fang ◽  
Zhanhong Liu ◽  
Pengbo Hou ◽  
Lijuan Cao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Human Muscle ◽  
Enzyme Linked Immunosorbent Assay ◽  
Muscle Stem Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory

Abstract Background Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. Methods The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. Results hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). Conclusion Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.

Abstract 17093: Human Neonatal Cardiac Mesenchymal Stem Cells Demonstrates Superior Cardiac Regenerative Abilities Compared to Other Stem Cells

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Muthukumar Gunasekaran ◽  
Rachana Mishra ◽  
Progyaparamita Saha ◽  
Xuebin Fu ◽  
Mohamed Abdullah ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Inflammatory Cytokines ◽  
Cell Types ◽  
Wild Type ◽  
Cell Type ◽  
Anti Inflammatory ◽  
Stem Cell Type

Stem cells transplantation is being explored as an effective therapy for heart diseases. However, majority of stem cell therapies for adult patients with myocardial infarction (MI) had mixed and inconsistent results implying chronological age may influence the effectiveness of regenerative therapies. Therefore, herein, we performed a head-to-head comparison between different, well-studied stem cell types to identify the superior regenerative cell type using rodent MI model.After our standard characterization for each stem cell type (FACS for cell surface markers), 1 million neonatal Cardiac Mesenchymal Stem cells (nMSCs), adult MSCs (aMSCs), adult derived cardiosphere derived cells (aCDCs), umbilical cord derived cells (UCBCs), Bone Marrow derived Mesenchymal Stem cells (BM-MSCs), or cell-free Iscove Modified Dulbecco Medium (IMDM as placebo control) were injected into athymic rat myocardial infarct model. Although all the tested groups significantly improved ejection fraction, nMSCs outperformed other stem cells in cardiac functional recovery. Additionally, nMSCs also showed significant increased cardiac functional recovery compared to aMSCs in wild type rat MI model. Mason trichrome staining with heart sections revealed that decreased fibrosis was evident on nMSCs injection compared to aMSCs in both athymic and wild type rat MI model. Myocardial sections from rats received nMSCs showed significantly reduced M1 macrophages (inflammatory) and increased M2 macrophages (anti-inflammatory) compared with sections from rats having received aMSCs and IMDM control. Pro and anti-inflammatory cytokines analyzed on sera collected on day 2 and 7 revealed that anti-inflammatory cytokine (IL10) was significantly increased and inflammatory cytokines (IL4 and IL12) reduced in nMSCs compared to aMSCs transplanted MI rat model.In conclusion, nMSCs demonstrated superior functional abilities, reduced fibrosis, inflammatory cells and cytokines compared to all the other cell types and with aMSCs demonstrating that nMSCs is an ideal stem cell type for therapeutic application in myocardial infarction.

scholarly journals 2542: Exosomes from mesenchymal stem cells package anti-inflammatory cytokines in allotransplantation

2016 ◽  
Vol 3 (1-2) ◽  
pp. 25-25
Author(s):  
Jonathan P. Massie ◽  
Yohei M. Rosen ◽  
J. Rodrigo Diaz-Siso ◽  
Natalie M. Plana ◽  
Daniel J. Ceradini
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Anti Inflammatory

scholarly journals 1,25(OH)2D3 Differently Affects Immunomodulatory Activities of Mesenchymal Stem Cells Depending on the Presence of TNF-α, IL-1β and IFN-γ

2019 ◽  
Vol 8 (12) ◽  
pp. 2211 ◽  
Author(s):  
Christian Behm ◽  
Alice Blufstein ◽  
Johannes Gahn ◽  
Barbara Kubin ◽  
Michael Nemec ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
T Lymphocyte ◽  
T Lymphocyte Proliferation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Necrosis Factor

Periodontal ligament-derived mesenchymal stem cells (hPDLSCs) possess immunomodulatory abilities which are strongly enhanced by various inflammatory cytokines. Vitamin D3 has anti-inflammatory effects on hPDLSCs and immune cells. However, no study to date has directly compared the influence of 1,25(OH)2D3 on the immunomodulatory activities of hPDLSCs in the presence of different cytokines. In the present study, the effects of hPDLSCs treated with tumor necrosis factor (TNF)-α, interleukin (IL)-1β, or interferon (IFN)-γ in the presence of 1,25(OH)2D3 on the proliferation of allogenic CD4+ T lymphocyte or on the functional status of primary CD68+ macrophages were analyzed in coculture models. Additionally, the effects of 1,25(OH)2D3 on TNF-α-, IL-1β-, and IFN-γ-induced gene expression of some immunomodulatory factors in hPDLSCs were compared. Under coculture conditions, 1,25(OH)2D3 increased or decreased CD4+ T lymphocyte proliferation via hPDLSCs, depending on the cytokine. hPDLSCs primed with 1,25(OH)2D3 and different cytokines affected pro- and anti-inflammatory cytokine expression in macrophages variably, depending on the priming cytokine. With one exception, 1,25(OH)2D3 significantly reduced TNF-α-, IL-1β-, and IFN-γ-induced expression of all the investigated immunomediators in hPDLSCs, albeit to different extents. These results suggest that 1,25(OH)2D3 influences the immunomodulatory activities of hPDLSCs depending qualitatively and quantitatively on the presence of certain inflammatory cytokines.

scholarly journals Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Tian Chen ◽  
Yamei Jiang ◽  
Shihao Xu ◽  
Yin Celeste Cheuk ◽  
Jiyan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pi3k Pathway ◽  
Poly I:C ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Objective: To investigate the effect and protective mechanism of mesenchymal stem cell subpopulations on acute kidney injury by establishing a mouse model of renal ischemia-reperfusion injury.Methods: Male C57BL/6 mice were randomly divided into five groups, namely, sham-operation group and those treated with normal saline, untreated mesenchymal stem cells, mesenchymal stem cells treated with lipopolysaccharide (LPS, pro-inflammatory phenotype) and mesenchymal stem cells treated with polyinosinic-polycytidylic acid (poly[I:C], anti-inflammatory phenotype) respectively. The renal function, histopathological damage, circulating inflammation levels and antioxidant capacity of mice were evaluated. The PI3 kinase p85 (PI3K) inhibitor was added into the conventional mesenchymal stem cell cultures in vitro to observe its effects on the secretion of anti-inflammatory cytokines.Results: Mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) could effectively reduce serum creatinine and blood urea nitrogen, attenuate histopathological damage and apoptosis level, decrease the level of circulating pro-inflammatory cytokines and increase the level of circulating anti-inflammatory cytokines, enhance peroxidase activity and reduce malondialdehyde content at each time point. After the addition of the PI3K inhibitor, the mRNA expression and protein secretion of indoleamine 2,3-dioxygenase 1 and heme oxygenase 1 of various mesenchymal stem cells were significantly reduced, and that of mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) was more obvious.Conclusions: Polyriboinosinic-polyribocytidylic acid (poly[I:C]), a synthetic double-stranded RNA, whose pretreatment induces mesenchymal stem cells to differentiate into the anti-inflammatory phenotype. Anti-inflammatory mesenchymal stem cells induced by poly(I:C) can better protect renal function, alleviate tissue damage, reduce circulating inflammation levels and enhance antioxidant capacity, and achieve stronger anti-inflammatory effects through the TLR3/PI3K pathway.

scholarly journals Enhancement of Anti-Inflammatory and Osteogenic Abilities of Mesenchymal Stem Cells via Cell-to-Cell Adhesion to Periodontal Ligament-Derived Fibroblasts

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Keita Suzuki ◽  
Naoyuki Chosa ◽  
Shunsuke Sawada ◽  
Naoki Takizawa ◽  
Takashi Yaegashi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Periodontal Ligament ◽  
Direct Contact ◽  
Cell Types ◽  
Stem Cell Markers ◽  
Periodontal Ligament Fibroblasts ◽  
Anti Inflammatory ◽  
Inflammatory Tissue

Mesenchymal stem cells (MSCs) are involved in anti-inflammatory events and tissue repair; these functions are activated by their migration or homing to inflammatory tissues in response to various chemokines. However, the mechanism by which MSCs interact with other cell types in inflammatory tissue remains unclear. We investigated the role of periodontal ligament fibroblasts (PDL-Fs) in regulating the anti-inflammatory and osteogenic abilities of bone marrow-derived- (BM-) MSCs. The expression of monocyte chemotactic protein- (MCP-)1 was significantly enhanced by stimulation of PDL-Fs with inflammatory cytokines. MCP-1 induced the migratory ability of BM-MSCs but not PDL-Fs. Expression levels of anti-inflammatory and inflammatory cytokines were increased and decreased, respectively, by direct-contact coculture between MSCs and PDL-Fs. In addition, the direct-contact coculture enhanced the expression of MSC markers that play important roles in the self-renewal and maintenance of multipotency of MSCs, which in turn induced the osteogenic ability of the cells. These results suggest that MCP-1 induces the migration and homing of BM-MSCs into the PDL inflammatory tissue. The subsequent adherence of MSCs to PDL-Fs plays an immunomodulatory role to terminate inflammation during wound healing and upregulates the expression stem cell markers to enhance the stemness of MSCs, thereby facilitating bone formation in damaged PDL tissue.

scholarly journals Cell Technologies in the Treatment of Chronic Wounds in Patients with Diabetes Mellitus

2021 ◽  
pp. 51-65
Author(s):  
Yu. V. Ivanova ◽  
S. M. Gramatiuk ◽  
V. O. Prasol ◽  
K. V. Miasoiedov ◽  
O. O. Zarudnyi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Chronic Wounds ◽  
Lower Extremities ◽  
Wound Surface ◽  
Average Hospital ◽  
Anti Inflammatory

Materials and methods. The results of treatment of 8 patients with chronic wounds and diabetes mellitus (DM) type 2 and stage IV chronic ischemia of the lower extremities by Fontaine were analyzed, in 2 cases there was a combination of venous and arterial insufficiency. Revascularization of the lower extremities was performed through open (2), endovascular (4) and hybrid surgery (2). In case of venous insufficiency, sclerotherapy of perforator veins was performed. After surgical treatment of the purulent focus, specific bacteriophages were used (after microflora identification). Hydrogel dressings were applied daily, alongside with transplantation of 5,000,000 mesenchymal stem cells (MSC) (CD73+, CD90+, CD105+ and CD45-, CD34-, CD14-, CD79-) by injection into muscle tissue around the wound, then the wound surface was closed with hMSC-fibroblast matrix. Results. After the closure of the wound surface with fibroblast matrix, the patients noted the disappearance of the pain syndrome. The surface area of the wounds averaged 91.3 ± 30.42 cm 2 before the start of treatment, 89.8 ± 34.21 cm 2 on day 5 and – 73.95 ± 21.2 cm 2 on day 12. Spontaneous epithelialization was achieved in the period from 35 to 141 days (depending on the initial state of the wounds). The average hospital stay was 22.6 ± 2.4 days. Discussion. It is known that human epithelial cells (hECs) and human mesenchymal stem cells (hMSCs) suppress proliferation, production of inflammatory cytokines and differentiation of T cells. At the same time, they stimulate the formation of regulatory T cells (Tregs). Soluble factors secreted by hECs, including PGE2, TGF-β, Fas-L, AFP, MIF, TRAIL and HLA-G, block differentiation of dendritic cells and M1 macrophages and promote differentiation of monocytes into the anti-inflammatory M2 phenotype. Moreover, hECs and hMSCs are known to be responsible for modulating the host immune system, mainly by suppressing TNF-α, IFN-γ, MCP-1 and IL-6 and increasing the level of anti-inflammatory cytokines. In vitro and in vivo results show increased cell migration and epithelialization leading to accelerated wound healing.

The impact of inflammatory licensing on heme oxygenase-1–mediated induction of regulatory T cells by human mesenchymal stem cells

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4826-4835 ◽  
Author(s):  
Dimitrios Mougiakakos ◽  
Regina Jitschin ◽  
C. Christian Johansson ◽  
Riki Okita ◽  
Rolf Kiessling ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Heme Oxygenase ◽  
Transforming Growth Factor ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Human Mscs ◽  
The Impact

Abstract Mesenchymal stem cells (MSCs) are characterized by their manifold immunomodulatory and regenerative properties. The stress-responsive, cytoprotective, and immunoregulatory molecule heme oxygenase-1 (HO-1) was recently identified as a key contributor for MSC-mediated suppression of alloactivated T cells. As HO-1 has also been implicated in the induction of regulatory T cells (Tregs), we sought to examine its impact on MSC-driven promotion of Tregs. Human MSCs were shown to induce, in a HO-1–dependent fashion, IL-10+ Tr1 and transforming growth factor-β+ Th3 Treg-subsets in allo- and T-cell receptor-activated lymphocytes. Because inflammatory stimuli modulate (“license”) human MSCs, we were interested in whether an in vitro alloreactive micro-milieu within mixed lymphocyte reactions (MLRs) alters the HO-1 expression. We observed a substantial down-regulation of HO-1 facilitated by yet unidentified soluble factor(s) produced in an MLR, and most probably occurring at the level of its major transcription-factor NF-E2–related factor 2. Interestingly, HO-1 lost its impact regarding suppressiveness, Treg induction, and promotion of IL-10 production for MSCs, which were prelicensed in an MLR environment. Taken together, we show that HO-1 produced by human MSCs beyond its direct suppressive function promotes formation of Tr1 and Th3 Tregs and IL-10 production, functions, which are taken over by other molecules, among them COX-2, after an alloreactive priming.

scholarly journals Mesenchymal Stem Cells Impact on COVID-19 Patients Immune System, an Ex Vivo Study

2021 ◽  
Author(s):  
Raedeh Saraei ◽  
kosar malekpour ◽  
Ali Hazrati ◽  
Hamed Valizadeh ◽  
Behnam Hashemi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Methylation Status ◽  
Lung Damage ◽  
Th2 Cells ◽  
Regulatory Function ◽  
Anti Inflammatory

Abstract Current clinical management approaches for COVID-19 patients are generally based on supportive treatment, which mainly includes respiratory support and restricted fluid input, which is currently a subject of much debate. Systemic Inflammation caused by SARS-CoV-2 may be related to various extrapulmonary comorbidities such as cytokine-mediated neuroinflammation leading to both non-neuronal and neurological consequences in COVID-19. Mesenchymal stem cells (MSCs) are adult stem cells with multipotent properties suitable for medical applications that have been reported as potential therapies in the setting of lung diseases. The immunosuppressive properties of MSCs provide a strong rationale to explore their potential beneficial effects on immune events in COVID-19. Multiple in vivo studies have demonstrated the capability of MSCs to prevent inflammatory responses and reduce lung damage. Recently, the use of MSCs in treating COVID-19 disease has improved long-term pulmonary function, but the specific mechanisms by which MSCs inhibit the severe inflammatory response induced by SARS-CoV-2 have not been elucidated. To the best of our knowledge, this is the first work describing the regulatory effects of MSCs on peripheral blood mononuclear cells (PBMCs) derived from patients with COVID-19 by measuring the pro-inflammatory and anti-inflammatory cytokines expression and secretion. We also examined the effects on the methylation of genes normally suppressed by DNA methylation in PBMCs. Our result showed that MSCs exerted an immune regulatory function on PBMCs in culture, skewing toward a type-2 response. This occurs by a mechanism consistent with a reduction in inflammatory factors (TNF-α, IL-1β, IL-6, IL-18, and IFNγ) protein and mRNA expression levels. In contrast, the anti-inflammatory cytokines (IL-4 and IL-10) increased following co-culture with MSCs. Consistent with these findings, the DNA methylation status of these immune genes seemed relevant to their expression pattern, except for GATA3, IL-1β, and IFNγ genes which showed no significant differences in methylation level between PBMCs with and without MSC exposure. Moreover, in co-culture interaction, MSCs modulated the Th1/Th2 cells in PBMCs compared to unstimulated PBMCs. These data demonstrate that MSCs can exert important immunomodulatory functions that affect virus-associated cytokine storms in pulmonary tissue during the severe respiratory stage.

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