scholarly journals Human Mesenchymal Stromal Cells Transplantation May Enhance or Inhibit 4T1 Murine Breast Adenocarcinoma through Different Approaches

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
T. Jazedje ◽  
A. L. Ribeiro ◽  
M. Pellati ◽  
H. M. de Siqueira Bueno ◽  
G. Nagata ◽  
...  

The use of Mesenchymal Stromal Cells (MSCs) aiming to treat cancer has shown very contradictory results. In an attempt to clarify the contradictory results reported in the literature and the possible role of human fallopian tube Mesenchymal Stromal Cells (htMSCs) against breast cancer, the aim of this study was to evaluate the clinical effect of htMSCs in murine mammary adenocarcinoma using two different approaches: (1) coinjections of htMSCs and 4T1 murine tumor cell lineage and (2) injections of htMSCs in mice at the initial stage of mammary adenocarcinoma development. Coinjected animals had a more severe course of the disease and a reduced survival, while tumor-bearing animals treated with 2 intraperitoneal injections of 106htMSCs showed significantly reduced tumor growth and increased lifespan as compared with control animals. Coculture of htMSCs and 4T1 tumor cells revealed an increase in IL-8 and MCP-1 and decreased VEGF production. For the first time, we show that MSCs isolated from a single source and donor when injected in the same animal model and tumor can lead to opposite results depending on the experimental protocol. Also, our results demonstrated that htMSCs can have an inhibitory effect on the development of murine mammary adenocarcinoma.

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 636
Author(s):  
Yoojin Seo ◽  
Tae-Hoon Shin ◽  
Ji-Su Ahn ◽  
Su-Jeong Oh ◽  
Ye Young Shin ◽  
...  

Mesenchymal stromal cells (MSCs) from various sources exhibit different potential for stemness and therapeutic abilities. Recently, we reported a unique MSCs from human palatine tonsil (TMSCs) and their superior proliferation capacity compared to MSCs from other sources. However, unique characteristics of each MSC are not yet precisely elucidated. We investigated the role of stanniocalcin-1 (STC1), an anti-oxidative hormone, in the functions of TMSCs. We found that STC1 was highly expressed in TMSC compared with MSCs from bone marrow or adipose tissue. The proliferation, senescence and differentiation of TMSCs were assessed after the inhibition of STC1 expression. STC1 inhibition resulted in a significant decrease in the proliferation of TMSCs and did not affect the differentiation potential. To reveal the anti-oxidative ability of STC1 in TMSCs themselves or against other cell types, the generation of mitochondrial reactive oxygen species (ROS) in TMSC or ROS-mediated production of interleukin (IL)-1β from macrophage-like cells were detected. Interestingly, the basal level of ROS generation in TMSCs was significantly elevated after STC1 inhibition. Moreover, down-regulation of STC1 impaired the inhibitory effect of TMSCs on IL-1β production in macrophages. Taken together, these findings indicate that STC1 is highly expressed in TMSCs and plays a critical role in proliferating and ROS-regulatory abilities.


2015 ◽  
Vol 39 (10) ◽  
pp. 1099-1110 ◽  
Author(s):  
Iordanis Pelagiadis ◽  
Eftichia Stiakaki ◽  
Christianna Choulaki ◽  
Maria Kalmanti ◽  
Helen Dimitriou

2021 ◽  
Author(s):  
Charlotte Sarre ◽  
Rafael Contreras Lopez ◽  
Nitirut Nerpernpisooth ◽  
Christian Barrere ◽  
Sarah Bahraoui ◽  
...  

Abstract Background: Mesenchymal Stromal Cells (MSC) have been widely used for their therapeutic properties in many clinical applications including myocardial infarction. Despite promising preclinical results and evidences of safety and efficacy in phases I/ II, inconsistencies in phase III trials have been reported. In a previous study, we have shown using MSC derived from the bone marrow of PPARβ/δ (Peroxisome proliferator-activated receptors β/δ) knockout mice that the acute cardioprotective properties of MSC during the first hour of reperfusion are PPARβ/δ-dependent but not related to the anti-inflammatory effect of MSC. However, the role of the modulation of PPARβ/δ expression on MSC cardioprotective and anti-apoptotic properties has never been investigated. Objectives: The aim of this study was to investigate the role of PPARβ/δ modulation (inhibition or activation) in MSC therapeutic properties in vitro and ex vivo in an experimental model of myocardial infarction.Methods and results: Naïve MSC and MSC pharmacologically activated or inhibited for PPARβ/δ were challenged with H202. Through specific DNA fragmentation quantification and qRT-PCR experiments, we evidenced in vitro an increased resistance to oxidative stress in MSC pre-treated by the PPARβ/δ agonist GW0742 versus naïve MSC. In addition, PPARβ/δ-priming allowed to reveal the anti-apoptotic effect of MSC on co-cultured cardiomyocytes. When injected during reperfusion in an ex vivo heart model of myocardial infarction, PPARβ/δ-primed MSC at a dose of 3.75x105 MSC/heart provided the same cardioprotective efficiency than 7.5x105 naïve MSC, identified as the optimal dose in our model. These enhanced short-term cardioprotective effects were associated with an increase in both anti-apoptotic effects and the number of MSC detected in the left ventricular wall at 1 hour of reperfusion. By contrast, inhibition of PPARβ/δ before their administration in post-ischemic hearts during reperfusion decreased their cardioprotective effects. Conclusion: Altogether these results revealed that PPARβ/δ-primed MSC exhibit an increased resistance to oxidative stress and enhanced anti-apoptotic properties on cardiac cells in vitro. PPARβ/δ-priming appears as an innovative strategy to enhance the cardioprotective effects of MSC and to decrease the injected doses. These results could be of major interest to improve MSC efficacy for the cardioprotection of injured myocardium in AMI patients.


2019 ◽  
Vol 7 ◽  
Author(s):  
Peng Hu ◽  
Qinxin Yang ◽  
Qi Wang ◽  
Chenshuo Shi ◽  
Dali Wang ◽  
...  

Abstact Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types, growth factors, extracellular matrix (ECM), nerves, and blood vessels. Mesenchymal stromal cells (MSCs) take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans. Exosomes, which are among the key products MSCs release, mimic the effects of parental MSCs. They can shuttle various effector proteins, messenger RNA (mRNA) and microRNAs (miRNAs) to modulate the activity of recipient cells, playing important roles in wound healing. Moreover, using exosomes avoids many risks associated with cell transplantation. Therefore, as a novel type of cell-free therapy, MSC-exosome -mediated administration may be safer and more efficient than whole cell. In this review, we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration. In addition, we address the hypothesis of MSCs microenvironment extracellular vesicles (MSCs-MEVs) or MSCs microenvironment exosomes (MSCs-MExos) that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications. This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.


Biomolecules ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 189 ◽  
Author(s):  
Elena Avdeeva ◽  
Elvira Shults ◽  
Tatyana Rybalova ◽  
Yaroslav Reshetov ◽  
Ekaterina Porokhova ◽  
...  

4-oxo-4H-pyran-2.6-dicarboxylic acid (chelidonic acid, ChA) in the native state and in the complex with calcium [Ca(ChA)(H2O)3], named saucalchelin (CaChA), was isolated from the extract of Saussurea controversa leaves for the first time for the Asteraceae family. The structure of ChA was determined by NMR, MS and confirmed by X-ray analysis of its monomethyl ester, and CaChA was described by IR, ICP-MS, CHN analysis. The yield of ChA and CaChA was 45 mg/g and 70 mg/g of extract, respectively. The osteogenic activity of ChA, n-monobutyl ester of chelidonic acid, and CaChA has been studied in vitro in a 21-day culture of human adipose-derived multipotent mesenchymal stromal cells (hAMMSCs) in a standard nutrient medium without osteogenic supplements. CaChA significantly stimulated the growth of cell mass and differentiation of hAMMSCs into osteoblasts with subsequent mineralization of the culture and it may be a promising substance for accelerating bone tissue regeneration and engineering.


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