International Journal of Molecular Sciences

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Dear Colleagues,

Mesenchymal stem cells (MSCs) are multipotent cells derived from various tissues including bone marrow and adipose tissues. MSCs have the capacity to differentiate into mesodermal lineages, including chondroblasts, osteoblasts, and adiocytes. Recently, novel tissue sources and various differentiation capacities of MSCs have been reported. However, progress in the clinical application and therapeutic use of MSCs is limited and further behind than expected. In the case of cell therapy using differentiated cells, the optimization of the quality of cell therapy candidates is very difficult. In addition to MSCs themselves, the importance of the characterization and therapeutic use of extracellular vesicles derived from MSCs has increased. This Special Issue will include studies on novel tissue sources for MSCs, the differentiation potential of MSCs derived from various sources, optimization of the quality of MSCs, including cells differentiated from MSCs, and other therapeutic candidates derived from MSCs, such as extracellular vesicles and MSC spheroids. In the case of therapeutic applications, the molecular characteristics of nondifferentiated/differentiated MSCs and their mode of action for clinical efficacy will be described.

Prof. Dr. Sung-Chul Jung
Guest Editor

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Keywords

mesenchymal stem cells
tissues
novel sources
differentiation
quality control
optimization
extracellular vesicles
secretome
spheroids
therapeutics

Published Papers (2 papers)

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Research

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13 pages, 2389 KiB

Open AccessArticle

SOCS3 Protein Mediates the Therapeutic Efficacy of Mesenchymal Stem Cells against Acute Lung Injury

by Young Eun Kim, Dong Kyung Sung, Yuna Bang, Se In Sung, Misun Yang, So Yoon Ahn and Yun Sil Chang

Int. J. Mol. Sci. 2023, 24(9), 8256; https://doi.org/10.3390/ijms24098256 - 4 May 2023

Cited by 1 | Viewed by 1475

Abstract

Mesenchymal stem cells (MSCs) have been studied as novel therapeutic agents because of their immunomodulatory properties in inflammatory diseases. The suppressor of cytokine signaling (SOCS) proteins are key regulators of the immune response and macrophage modulation. In the present study, we hypothesized that SOCS in MCSs might mediate macrophage modulation and tested this in a bacteria-induced acute lung injury (ALI) mouse model. The macrophage phenotype was observed in RAW264.7 alveolar macrophages exposed to lipopolysaccharide (LPS) in an in vitro model, and in the ALI mouse model induced by tracheal administration of Escherichia coli (1 × 10⁷ CFU in 0.05mL PBS). In LPS-exposed RAW264.7 cells, the levels of markers of M1 macrophages, such as CD86 and pro-inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α), significantly increased, but they significantly reduced after MSC treatment. Meanwhile, the levels of markers of M2 macrophages, such as CD204 and anti-inflammatory cytokines (IL-4 and IL-10), increased after LPS exposure, and further significantly increased after MSC treatment. This regulatory effect of MSCs on M1/M2 macrophage polarization was significantly abolished by SOCS3 inhibition. In the E. coli-induced ALI model, tissue injury and inflammation in the mouse lung were significantly attenuated by the transplantation of MSCs, but not by SOCS3-inhibited MSCs. The regulatory effect of MSCs on M1/M2 macrophage polarization was observed in the lung injury model but was significantly abolished by SOCS3 inhibition. Taken together, our findings suggest that SOCS3 is an important mediator for macrophage modulation in anti-inflammatory properties of MSCs. Full article

(This article belongs to the Special Issue New Sources, Differentiation, and Therapeutic Uses of Mesenchymal Stem Cells 3.0)

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Review

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36 pages, 2317 KiB

Open AccessReview

miRNA-Guided Regulation of Mesenchymal Stem Cells Derived from the Umbilical Cord: Paving the Way for Stem-Cell Based Regeneration and Therapy

by Arsinoe C. Thomaidou, Maria Goulielmaki, Antonis Tsintarakis, Panagiotis Zoumpourlis, Marialena Toya, Ioannis Christodoulou and Vassilis Zoumpourlis

Int. J. Mol. Sci. 2023, 24(11), 9189; https://doi.org/10.3390/ijms24119189 - 24 May 2023

Cited by 3 | Viewed by 3061

Abstract

The human body is an abundant source of multipotent cells primed with unique properties that can be exploited in a multitude of applications and interventions. Mesenchymal stem cells (MSCs) represent a heterogenous population of undifferentiated cells programmed to self-renew and, depending on their origin, differentiate into distinct lineages. Alongside their proven ability to transmigrate toward inflammation sites, the secretion of various factors that participate in tissue regeneration and their immunoregulatory function render MSCs attractive candidates for use in the cytotherapy of a wide spectrum of diseases and conditions, as well as in different aspects of regenerative medicine. In particular, MSCs that can be found in fetal, perinatal, or neonatal tissues possess additional capabilities, including predominant proliferation potential, increased responsiveness to environmental stimuli, and hypoimmunogenicity. Since microRNA (miRNA)-guided gene regulation governs multiple cellular functions, miRNAs are increasingly being studied in the context of driving the differentiation process of MSCs. In the present review, we explore the mechanisms of miRNA-directed differentiation of MSCs, with a special focus on umbilical cord-derived mesenchymal stem cells (UCMSCs), and we identify the most relevant miRNAs and miRNA sets and signatures. Overall, we discuss the potent exploitations of miRNA-driven multi-lineage differentiation and regulation of UCMSCs in regenerative and therapeutic protocols against a range of diseases and/or injuries that will achieve a meaningful clinical impact through maximizing treatment success rates, while lacking severe adverse events. Full article

(This article belongs to the Special Issue New Sources, Differentiation, and Therapeutic Uses of Mesenchymal Stem Cells 3.0)

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