Mesenchymal Stem Cells Induced In Vitro Generation of Antigen Specific Regulatory T-Cells Containing CD4+CD8+ Population: A Cell-Based Therapy To Promote Transplantation Tolerance.

2014 ◽  
Vol 98 ◽  
pp. 232
Author(s):  
S. Dave ◽  
A. Vanikar ◽  
H. Trivedi
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Transplantation Tolerance ◽  
Cell Based Therapy ◽  
A Cell

scholarly journals Mesenchymal Stem Cell–Derived Extracellular Vesicles Induce Regulatory T Cells to Ameliorate Chronic Kidney Injury

Hypertension ◽  
2020 ◽  
Vol 75 (5) ◽  
pp. 1223-1232 ◽  
Author(s):  
Turun Song ◽  
Alfonso Eirin ◽  
Xiangyang Zhu ◽  
Yu Zhao ◽  
James D. Krier ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Extracellular Vesicles ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Activated T Cells ◽  
Anti Inflammatory

Metabolic syndrome (MetS) profoundly changes the contents of mesenchymal stem cells and mesenchymal stem cells–derived extracellular vesicles (EVs). The anti-inflammatory TGF-β (transforming growth factor-β) is selectively enriched in EVs from Lean but not from MetS pigs, but the functional impact of this endowment remains unknown. We hypothesized that Lean-EVs more effectively induce regulatory T cells in injured kidneys. Five groups of pigs (n=7 each) were studied after 16 weeks of diet-induced MetS and unilateral renal artery stenosis (RAS; MetS+RAS). Two groups of MetS+RAS were treated 4 weeks earlier with an intrarenal injection of either Lean-EVs or MetS-EVs. MetS+RAS had lower renal volume, renal blood flow, and glomerular filtration rate than MetS pigs. Compared with Lean-EVs, MetS-EVs were less effective in improving renal function and decreasing tubular injury and fibrosis in MetS+RAS. Lean-EVs upregulated TGF-β expression in stenotic kidney and increased regulatory T cells numbers more prominently. Furthermore, markedly upregulated anti-inflammatory M2 macrophages reduced proinflammatory M1 macrophages, and CD8 + T cells were detected in stenotic kidneys treated with Lean-EVs compared with MetS-EVs, and renal vein levels of interleukin-1β were reduced. In vitro, coculture of Lean-EVs with activated T cells led to greater TGF-β-dependent regulatory T cells induction than did MetS-EVs. Therefore, the beneficial effects of mesenchymal stem cells–derived EVs on injured kidneys might be partly mediated by their content of TGF-β signaling components, which permitting increased Treg preponderance. Modulating EV cargo and transforming their functionality might be useful for renal repair.

scholarly journals On the interactions between mesenchymal stem cells and regulatory T cells for immunomodulation in transplantation

2012 ◽  
Vol 3 ◽  
Author(s):  
Anja U. Engela ◽  
Carla C. Baan ◽  
Frank J. M. F. Dor ◽  
Willem Weimar ◽  
Martin J. Hoogduijn
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells

Mesenchymal stem cells induce the expansion of regulatory T cells in abortion-prone mice

Reproduction ◽  
2021 ◽  
Author(s):  
Amir Salek Farrokhi ◽  
Amir-Hassan Zarnani ◽  
Fatemeh Rezaei kahmini ◽  
Seyed Mohammad Moazzeni
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
De Novo ◽  
Abortion Rate ◽  
Cellular Mechanisms ◽  
Inguinal Lymph Nodes

Recurrent pregnancy loss (RPL) is one of the most common complications of early pregnancy associated in most cases with local or systemic immune abnormalities such as the diminished proportion of regulatory T cells (Tregs). Mesenchymal stem cells (MSCs) have been shown to modulate immune responses by de novo induction and expansion of Tregs. In this study, we analyzed the molecular and cellular mechanisms involved in Treg-associated pregnancy protection following MSCs administration in an abortion-prone mouse mating. In a case-control study, syngeneic abdominal fat-derived MSCs were administered intraperitoneally (i.p) to the DBA/2-mated CBA/J female mice on day 4.5 of pregnancy. Abortion rate, Tregs proportion in spleen and inguinal lymph nodes, and Ho1, Foxp3, Pd1, and Ctla4 genes expression at the feto-maternal interface were then measured on day 13.5 of pregnancy using flow cytometry and quantitative RT- PCR, respectively. The abortion rate in MSCs-treated mice was significantly reduced and normalized to the level observed in normal pregnant animals. We demonstrated a significant induction of Tregs in inguinal lymph nodes but not in the spleen following MSCs administration. Administration of MSCs remarkably upregulated the expression of HO1, Foxp3, Pd1, and Ctla4 genes in both placenta and decidua. Here, we show that MSCs therapy could protect the fetus in the abortion-prone mice through Tregs expansion and up-regulation of Treg-related genes. These events could establish an immune-privileged microenvironment, which participates in regulation of detrimental maternal immune responses against the semi-allogeneic fetus.

scholarly journals Effect of Human Mesenchymal Stem Cells on Xenogeneic T and B Cells Isolated from Lupus-Prone MRL.Faslpr Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hong Kyung Lee ◽  
Eun Young Kim ◽  
Hyung Sook Kim ◽  
Eun Jae Park ◽  
Hye Jin Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Human Mesenchymal Stem Cells ◽  
Preclinical Studies ◽  
Dependent Manner ◽  
T And B Cells

Systemic lupus erythematosus (SLE) is an autoimmune disease, which is characterized by hyperactivation of T and B cells. Human mesenchymal stem cells (hMSCs) ameliorate the progression of SLE in preclinical studies using lupus-prone MRL.Faslpr mice. However, whether hMSCs inhibit the functions of xenogeneic mouse T and B cells is not clear. To address this issue, we examined the in vitro effects of hMSCs on T and B cells isolated from MRL.Faslpr mice. Naïve hMSCs inhibited the functions of T cells but not B cells. hMSCs preconditioned with IFN-γ (i) inhibited the proliferation of and IgM production by B cells, (ii) attracted B cells for cell–cell interactions in a CXCL10-dependent manner, and (iii) inhibited B cells by producing indoleamine 2,3-dioxygenase. In summary, our data demonstrate that hMSCs exert therapeutic activity in mice in three steps: first, naïve hMSCs inhibit the functions of T cells, hMSCs are then activated by IFN-γ, and finally, they inhibit B cells.

scholarly journals Human Periapical Cyst-Derived Stem Cells Can Be A Smart “Lab-on-A-Cell” to Investigate Neurodegenerative Diseases and the Related Alteration of the Exosomes’ Content

2019 ◽  
Vol 9 (12) ◽  
pp. 358 ◽  
Author(s):  
Tatullo ◽  
Codispoti ◽  
Spagnuolo ◽  
Zavan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Circadian Rhythm ◽  
Neurodegenerative Diseases ◽  
Clock Genes ◽  
Experimental Studies ◽  
Cell Aging ◽  
A Cell ◽  
Periapical Cyst

Promising researches have demonstrated that the alteration of biological rhythms may be consistently linked to neurodegenerative pathologies. Parkinson’s disease (PD) has a multifactorial pathogenesis, involving both genetic and environmental and/or molecular co-factors. Generally, heterogeneous alterations in circadian rhythm (CR) are a typical finding in degenerative processes, such as cell aging and death. Although numerous genetic phenotypes have been discovered in the most common forms of PD, it seems that severe deficiencies in synaptic transmission and high vesicular recycling are frequently found in PD patients. Neuron-to-neuron interactions are often ensured by exosomes, a specific type of extracellular vesicle (EV). Neuron-derived exosomes may carry several active compounds, including miRNAs: Several studies have found that circulating miRNAs are closely associated with an atypical oscillation of circadian rhythm genes, and they are also involved in the regulation of clock genes, in animal models. In this context, a careful analysis of neural-differentiated Mesenchymal Stem Cells (MSCs) and the molecular and genetic characterization of their exosome content, both in healthy cells and in PD-induced cells, could be a strategic field of investigation for early diagnosis and better treatment of PD and similar neurodegenerative pathologies. A novel MSC population, called human periapical cyst–mesenchymal stem cells (hPCy–MSCs), has demonstrated that it naively expresswa the main neuronal markers, and may differentiate towards functional neurons. Therefore, hPCy–MSCs can be considered of particular interest for testing of in vitro strategies to treat neurological diseases. On the other hand, the limitations of using stem cells is an issue that leads researchers to perform experimental studies on the exosomes released by MCSs. Human periapical cyst-derived mesenkymal stem cells can be a smart “lab-on-a-cell” to investigate neurodegenerative diseases and the related exosomes’ content alteration.

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