Effect of Preconditioned Mesenchymal Stromal Cells on Early Microvascular Disturbance in a Mouse Sepsis Model

Baudry, Nathalie; Starck, Julie; Aussel, Claude; Lund, Kyle; Aletti, M.; Duranteau, Jacques; Banzet, Sébastien; Lataillade, Jean‐Jacques; Vicaut, Éric; Peltzer, Juliette

doi:10.1089/scd.2019.0134

Cited by 13 publications

(14 citation statements)

References 40 publications

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“…Numerous primings have been studied, including inflammatory (TNFα, IFNγ, IL1β) or hypoxic conditions (Andreeva et al, 2017). IFNγ preconditioning has been widely studied and improved MSC efficacy in models where an immunomodulatory effect of MSC is expected, such as graft versus host disease (Polchert et al, 2008;Tobin et al, 2013), colitis (Duijvestein et al, 2011), or sepsis (Baudry et al, 2019). A well-documented effect of both inflammatory and hypoxic FIGURE 3 | (A) Significantly altered miRNA levels in extracellular vesicles of Control, Hypoxia, and Interferon-treated MSC are shown.…”

Section: Effect Of Primingmentioning

confidence: 99%

“…Therefore, hypoxia (HYP) priming has been successfully used for MSC treatment in ischemic diseases (Leroux et al, 2010;Jaussaud et al, 2013;Zhang et al, 2019), improving both survival and function (Chacko et al, 2010;Peterson et al, 2011;Beegle et al, 2015;Feng and Wang, 2017;Elabd et al, 2018). Similarly, inflammatory priming with TNFα, IL1β, or interferon gamma (IFNγ) priming increase the immunomodulatory properties of MSC in vitro and in vivo (English et al, 2007;Chinnadurai et al, 2014;Cassano et al, 2018;Baudry et al, 2019;Magne et al, 2020). Thus, MSC priming is currently considered an important way to improve MSC function or get rid of inter-individual variability.…”

Section: Introductionmentioning

confidence: 99%

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Interferon-γ and Hypoxia Priming Have Limited Effect on the miRNA Landscape of Human Mesenchymal Stromal Cells-Derived Extracellular Vesicles

Peltzer

Lund²,

Goriot

et al. 2020

Front. Cell Dev. Biol.

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Mesenchymal stromal cell (MSC)-based cell therapy has received great interest in regenerative medicine. Priming the cells during the culture phase can improve their efficacy and/or survival after injection. The literature suggests that MSC extracellular vesicles (EV) can recapitulate a substantial part of the beneficial effects of the cells they originate from, and that micro-RNAs (miRNAs) are important players in EV biological action. Here, our aim was to determine if two classical priming methods of MSC, interferon-gamma (IFNγ) and hypoxia (HYP), could modify their EV miRNA content. Human bone marrow MSCs (BM-MSCs) from five healthy donors were cultured with IFNγ or in HYP or in control (CONT) conditions. The conditioned media were collected after 48 h in serum-free condition and EV were isolated by ultracentrifugation. Total RNA was isolated, pools of CONT, IFN, and HYP cDNA were prepared, and a miRNA profiling was performed using RT-qPCR. Then, miRNAs were selected based on their detectability and measured on each individual EV sample. Priming had no effect on EV amount or size distribution. A set of 81 miRNAs was detected in at least one of the pools of EVs. They were measured on each individual sample; 41 miRNAs were detected in all samples. The principal component analysis (PCA) failed to discriminate the groups. HYP induced a significant decrease in EV hsa-miR-34a-3p content and IFN induced a significant increase in five miRNAs (hsa-miR-25-3p, hsa-miR-106a-5p, hsa-miR-126-3p, hsa-miR-451a, and hsa-miR-665). Taken together, we found only limited alterations in the miRNA landscape of MSC EV with a high inter-individual variability.

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Section: Effect Of Primingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interferon-γ and Hypoxia Priming Have Limited Effect on the miRNA Landscape of Human Mesenchymal Stromal Cells-Derived Extracellular Vesicles

Peltzer

Lund²,

Goriot

et al. 2020

Front. Cell Dev. Biol.

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“…In sepsis endothelial dysfunction is believed to have a role in microvascular disturbance and MSCs may have a protective role in regulating this. In a murine intraperitoneal sepsis model, administration of IFN-γ preconditioned MSCs reduced leukocyte adherence to the endothelium, increased leucocyte flow through the microvasculature, and increased the velocity of red blood cell flow through the microvasculature [77]. In this model, plasma levels of E-selectin, a leucocyte-endothelial cell adhesion molecule, were reduced by naïve and IFN-γ preconditioned MSCs.…”

Section: Reparative Effectsmentioning

confidence: 80%

“…In this model, plasma levels of E-selectin, a leucocyte-endothelial cell adhesion molecule, were reduced by naïve and IFN-γ preconditioned MSCs. Plasma ICAM-1, another adhesion molecule, was increased by IFN-γ preconditioned MSCs, and it is postulated this may have a protective effect on leukocyte adhesion by competing with membrane-bound ICAM-1 [77].…”

Section: Reparative Effectsmentioning

confidence: 99%

“…Horie et al, 2020, demonstrated in a rodent VILI model, MSCs primed with a combination of cytokines (IL-1β, TNF-α, and IFN-γ) enhanced resolution of histological evidence of VILI, restored oxygenation, improved lung compliance, and reduced lung edema [145]. Baudry et al, 2019, demonstrated that IFN-γ preconditioned MSCs, in a murine sepsis model, had beneficial effects on the microcirculation by increasing the flow of leucocytes, decreasing leucocyte adhesion, and increasing red blood cell velocity [77].…”

Section: Preconditioning To Enhance Msc Activity (Summary Table 5)mentioning

confidence: 99%

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Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: optimizing the therapeutic potential

Gorman

Millar

O’Kane

2020

Expert Review of Respiratory Medicine

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Introduction: Mesenchymal stromal (stem) cell (MSC) therapies are emerging as a promising therapeutic intervention in patients with Acute Respiratory Distress Syndrome (ARDS) and sepsis due to their reparative, immunomodulatory, and antimicrobial properties. Areas covered: This review provides an overview of Mesenchymal stromal cells (MSCs) and their mechanisms of effect in ARDS and sepsis. The preclinical and clinical evidence to support MSC therapy in ARDS and sepsis is discussed. The potential for MSC therapy in COVID-19 ARDS is discussed with insights from respiratory viral models and early clinical reports of MSC therapy in COVID-19. Strategies to optimize the therapeutic potential of MSCs in ARDS and sepsis are considered including preconditioning, altered gene expression, and alternative cell-free MSC-derived products, such as extracellular vesicles and conditioned medium. Expert opinion: MSC products present considerable therapeutic promise for ARDS and sepsis. Preclinical investigations report significant benefits and early phase clinical studies have not highlighted safety concerns. Optimization of MSC function in preclinical models of ARDS and sepsis has enhanced their beneficial effects. MSC-derived products, as cell-free alternatives, may provide further advantages in this field. These strategies present opportunity for the clinical development of MSCs and MSC-derived products with enhanced therapeutic efficacy.

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First Clinical Experiences Using Preconditioning Approaches to Improve MSC-Based Therapies

Le,

Cressman,

Morales

et al. 2024

Curr Stem Cell Rep

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Purpose of Review Describe the rationale for preconditioning MSCs prior to use as therapy and the state-of-the-art of using preconditioning of MSCs in clinical settings. Recent Findings Mounting preclinical data supports preconditioning of mesenchymal stromal cells (MSCs) to enhance their therapeutic efficacy. Most research has focused on cytokine priming and hypoxic preconditioning, while other approaches, such as glycoengineering, remain relatively understudied. Despite strong preclinical data, clinical evidence supporting preconditioning strategies are limited to six Phase I clinical trials (most of them in progress). Summary Here, we succinctly discuss the rationale for preconditioning using cytokines, hypoxia, and glycoengineering, while elaborating on the respective clinical experiences. Overall, we note that preconditioning is highly dependent on the desired application, and therefore requires elucidating the mechanism of action of the MSCs used for therapy. Preconditioning may also help mitigate heterogeneity of MSC lots. Based on the remarkable safety profile of MSCs, even when used in allogeneic settings, the role of preconditioning prior to their final formulation might be the key to reach expected therapeutic outcomes.

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Effect of Preconditioned Mesenchymal Stromal Cells on Early Microvascular Disturbance in a Mouse Sepsis Model

Cited by 13 publications

References 40 publications

Interferon-γ and Hypoxia Priming Have Limited Effect on the miRNA Landscape of Human Mesenchymal Stromal Cells-Derived Extracellular Vesicles

Interferon-γ and Hypoxia Priming Have Limited Effect on the miRNA Landscape of Human Mesenchymal Stromal Cells-Derived Extracellular Vesicles

Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: optimizing the therapeutic potential

First Clinical Experiences Using Preconditioning Approaches to Improve MSC-Based Therapies

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