Possible Role of Prep1 Homeodomain Transcription Factor in Cardiac Mesenchymal Stromal Cells

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.

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Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration

Burns & Trauma ◽

10.1186/s41038-019-0178-8 ◽

2019 ◽

Vol 7 ◽

Cited By ~ 15

Author(s):

Peng Hu ◽

Qinxin Yang ◽

Qi Wang ◽

Chenshuo Shi ◽

Dali Wang ◽

...

Keyword(s):

Wound Healing ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Messenger Rna ◽

Cell Types ◽

Skin Wound ◽

Effector Proteins ◽

Skin Wound Healing ◽

New Research

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.

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A Protocol for the Isolation, Culture, and Cryopreservation of Umbilical Cord-Derived Canine Mesenchymal Stromal Cells: Role of Cell Attachment in Long-Term Maintenance

Stem Cells and Development ◽

10.1089/scd.2019.0145 ◽

2020 ◽

Vol 29 (11) ◽

pp. 695-713 ◽

Cited By ~ 1

Author(s):

Adrienne Wright ◽

Larry Snyder ◽

Kaori Knights ◽

Hong He ◽

Nora L. Springer ◽

...

Keyword(s):

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Cell Attachment ◽

Term Maintenance

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The Role of Mesenchymal Stromal Cells in the Management of Osteoarthritis of the Knee

Update on Mesenchymal and Induced Pluripotent Stem Cells ◽

10.5772/intechopen.86016 ◽

2020 ◽

Cited By ~ 1

Author(s):

Charan Thej ◽

Pawan Kumar Gupta

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Osteoarthritis Of The Knee

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

Stem Cells International ◽

10.1155/2015/796215 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

T. Jazedje ◽

A. L. Ribeiro ◽

M. Pellati ◽

H. M. de Siqueira Bueno ◽

G. Nagata ◽

...

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Cell Lineage ◽

Inhibitory Effect ◽

Mammary Adenocarcinoma ◽

Breast Adenocarcinoma ◽

Human Fallopian Tube ◽

Initial Stage ◽

First Time

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.

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