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New Sources, Differentiation, and Therapeutic Uses of Mesenchymal Stem Cells...
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New Sources, Differentiation, and Therapeutic Uses of Mesenchymal Stem Cells 3.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 7133

Special Issue Editor

Prof. Dr. Sung-Chul Jung

E-Mail Website
Guest Editor
Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea
Interests: cell therapy; differentiation; muscle; lysosomal storage disease; Schwann cells; peripheral neuropathy; mesenchymal stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

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

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Published Papers (3 papers)

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Research

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18 pages, 6315 KiB  
Article
Mesenchymal Stem Cells Derived from Human Urine-Derived iPSCs Exhibit Low Immunogenicity and Reduced Immunomodulatory Profile
by Peiyun Wang, Ying Zhang, Zhixing Li, Shenglan Zhou, Qiyu Tang, Zujia Wang, Rou Xiao, Mai Feng, Lingqian Wu and Desheng Liang
Int. J. Mol. Sci. 2024, 25(19), 10394; https://doi.org/10.3390/ijms251910394 - 27 Sep 2024
Viewed by 1006
Abstract
Human-induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) represent a promising and renewable cell source for therapeutic applications. A systematic evaluation of the immunological properties and engraftment potential of iMSCs generated from urine-derived iPSCs is lacking, which has impeded their broader application. [...] Read more.
Human-induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) represent a promising and renewable cell source for therapeutic applications. A systematic evaluation of the immunological properties and engraftment potential of iMSCs generated from urine-derived iPSCs is lacking, which has impeded their broader application. In this study, we differentiated urine-derived iPSCs into iMSCs and assessed their fundamental MSC characteristics, immunogenicity, immunomodulatory capacity and in vivo engraftment. Compared to umbilical cord-derived MSCs (UCMSCs), iMSCs demonstrated an enhanced proliferative capacity, a higher level of regenerative gene expression, and lower immunogenicity, strengthening resistance to apoptosis induced by allogeneic peripheral blood mononuclear cells (PBMCs) and the NK-92 cell line. In addition, iMSCs exhibited a diminished ability to inhibit T cell proliferation and activation compared with UCMSCs. Transcriptomic analyses further revealed the decreased expression of immune regulatory factors in iMSCs. After transfusion into mouse models, iMSCs engrafted in the lungs, liver, and spleen and exhibited the ability to migrate to tumor tissues. Our results indicated that iMSCs generated from urine-derived iPSCs have a significant replicative capacity, low immunogenicity and unique immunomodulatory properties, and hence offer obvious advantages in immune privilege and allogenic therapeutic application prospects. 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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13 pages, 2389 KiB  
Article
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 5 | Viewed by 1878
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 [...] Read more.
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  
Review
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 8 | Viewed by 3917
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 [...] Read more.
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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