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Recent Developments in Mesenchymal Stem Cells

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Dear Colleagues,

Mesenchymal-stromal-cell-based products are among the cutting-edge biological approaches for regenerative medicine in several fields of medical technology. Alongside the classical view of clinically expanded cells, mesenchymal stromal cells are now envisioned as crucial biological products acting as the active force in more complex therapeutic agents such as orthobiologics. Additionally, outmatching the idea of tissue substitution, mesenchymal stromal cells are a reservoir of active factors and extracellular vesicles, collectively referred to as the “secretome”, that stimulate resident progenitor cells to favour tissue regeneration. For these reasons, both cells and their secretomes are the biological platforms of advanced therapeutics, which are attracting great interest in regenerative medicine approaches.

This Special Issue aims to identify the advances required to address future regenerative-medicine-based approaches relying on mesenchymal stromal cells and their released products. This Special Issue will establish the benchmarks for the state-of-the-art evidence necessary to facilitate the clinical implementation of these innovative therapeutic approaches. Reports presenting basic science, in vitro, in vivo and pre-clinical research may be included to ensure that regenerative medicine technology is able to be seamlessly transferred to the clinic.

Dr. Antonietta Rosa Silini
Dr. Enrico Ragni
Guest Editors

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Keywords

mesenchymal stromal cell
regenerative medicine
secretome

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18 pages, 3013 KiB

Open AccessArticle

TSG-6 Inhibits the NF-κB Signaling Pathway and Promotes the Odontogenic Differentiation of Dental Pulp Stem Cells via CD44 in an Inflammatory Environment

by Ying Wang, Yulang Xie, Ningning Xue, Hao Xu, Dunfang Zhang, Ning Ji and Qianming Chen

Biomolecules 2024, 14(3), 368; https://doi.org/10.3390/biom14030368 - 19 Mar 2024

Viewed by 869

Abstract

In pulpitis, dentinal restorative processes are considerably associated with undifferentiated mesenchymal cells in the pulp. This study aimed to investigate strategies to improve the odonto/osteogenic differentiation of dental pulp stem cells (DPSCs) in an inflammatory environment. After pretreatment of DPSCs with 20 ng/mL tumor necrosis factor-induced protein-6 (TSG-6), DPSCs were cultured in an inflammation-inducing solution. Real-time polymerase chain reaction and Western blotting were performed to measure the expression levels of nuclear factor kappa B (NF-κB) and odonto/osteogenic differentiation markers, respectively. Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays were used to assess cell proliferation and activity. Subcutaneous ectopic osteogenesis and mandibular bone cultures were performed to assess the effects of TSG-6 in vivo. The expression levels of odonto/osteogenic markers were higher in TSG-6-pre-treated DPSCs than nontreated DPSCs, whereas NF-κB-related proteins were lower after the induction of inflammation. An anti-CD44 antibody counteracted the rescue effect of TSG-6 on DPSC activity and mineralization in an inflammatory environment. Exogenous administration of TSG-6 enhanced the anti-inflammatory properties of DPSCs and partially restored their mineralization function by inhibiting NF-κB signaling. The mechanism of action of TSG-6 was attributed to its interaction with CD44. These findings reveal novel mechanisms by which DPSCs counter inflammation and provide a basis for the treatment of pulpitis. Full article

(This article belongs to the Special Issue Recent Developments in Mesenchymal Stem Cells)

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23 pages, 11147 KiB

Open AccessArticle

Comparison between the Regenerative and Therapeutic Impacts of Bone Marrow Mesenchymal Stem Cells and Adipose Mesenchymal Stem Cells Pre-Treated with Melatonin on Liver Fibrosis

by Ahmed Elzainy, Abir El Sadik and Waleed Mohammad Altowayan

Biomolecules 2024, 14(3), 297; https://doi.org/10.3390/biom14030297 - 01 Mar 2024

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Abstract

Background: The distinctive feature of liver fibrosis is the progressive replacement of healthy hepatic cells by the extracellular matrix protein, which is abundant in collagen I and III, with impaired matrix remodeling. The activation of myofibroblastic cells enhances the fibrogenic response of complex interactions of hepatic stellate cells, fibroblasts, and inflammatory cells to produce the excessive deposition of the extracellular protein matrix. This process is activated by multiple fibrogenic mediators and cytokines, such as TNF-α and IL-1β, accompanied with a decrease in the anti-fibrogenic factor NF-κβ. Mesenchymal stem cells (MSCs) represent a promising therapy for liver fibrosis, allowing for a more advanced regenerative influence when cultured with extrinsic or intrinsic proliferative factors, cytokines, antioxidants, growth factors, and hormones such as melatonin (MT). However, previous studies showed conflicting findings concerning the therapeutic effects of adipose (AD) and bone marrow (BM) MSCs; therefore, the present work aimed to conduct a comparative and comprehensive study investigating the impact of MT pre-treatment on the immunomodulatory, anti-inflammatory, and anti-apoptotic effects of AD- and BM-MSCs and to critically analyze whether MT-pre-treated AD-MSCs and BM-MSCs reveal equal or different therapeutic and regenerative potentials in a CCl4-injured liver experimental rat model. Materials and methods: Six groups of experimental rats were used, with ten rats in each group: group I (control group), group II (CCl4-treated group), group III (CCl4- and BM-MSC-treated group), group IV (CCl4 and MT-pre-treated BM-MSC group), group V (CCl4- and AD-MSC-treated group), and group VI (CCl4 and MT-pre-treated AD-MSC group). Liver function tests and the gene expression of inflammatory, fibrogenic, apoptotic, and proliferative factors were analyzed. Histological and immunohistochemical changes were assessed. Results: The present study compared the ability of AD- and BM-MSCs, with and without MT pre-treatment, to reduce hepatic fibrosis. Both types of MSCs improved hepatocyte function by reducing the serum levels of ALT, aspartate aminotransferase (AST), alkaline phosphatase (AKP), and total bilirubin (TBIL). In addition, the changes in the hepatocellular architecture, including the hepatocytes, liver sinusoids, central veins, portal veins, biliary ducts, and hepatic arteries, showed a decrease in hepatocyte injury and cholestasis with a reduction in inflammation, apoptosis, and necrosis of the hepatic cells, together with an inhibition of liver tissue fibrosis. These results were augmented by an analysis of the expression of the pro-inflammatory cytokines TNFα and IL-1β, the anti-fibrogenic factor NF-κβ, the apoptotic factor caspase-3, and the proliferative indicators antigen Ki-67 and proliferating cell nuclear antigen (PCNA). These findings were found to be statistically significant, with the restoration of normal parameters in the rats that received AD-MSCs pre-treated with MT, denoting optimal regenerative and therapeutic effects. Conclusions: AD-MSCs pre-treated with MT are the preferred choice in improving hepatic fibrosis and promoting the therapeutic and regenerative ability of liver tissue. They represent a very significant tool for future stem cell use in the tissue regeneration strategy for the treatment of liver diseases. Full article

(This article belongs to the Special Issue Recent Developments in Mesenchymal Stem Cells)

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