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Cells
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Study on Human Mesenchymal Stem Cells
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Study on Human Mesenchymal Stem Cells

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 10160

Special Issue Editor

Dr. Michela Noseda

E-Mail Website
Guest Editor
National Heart and Lung Institute, Imperial College London, London, UK
Interests: heart failure; ischemic cardiomyopathy; cardiac regeneration and repair

Special Issue Information

Dear Colleagues, 

Mesenchymal stem cells (MSCs) are a group of multipotent cells of mesodermal origin. They were originally obtained from bone marrow, although MSC-like cells were subsequently derived from other tissues, including the placenta, umbilical cord, adipose tissue, skeletal muscle, and corneal stroma. Despite being used in hundreds of clinical trials, their retrospective derivation in culture poses challenges in understanding their anatomical identity, phenotype, tissue localization, and biological functions. Although differentiation in specific lineages can avail the stem cell characteristics of MSCs contributing to tissue regeneration, MSCs via paracrine and juxtracrine mechanisms mediated by immunomodulatory and growth factors pinpoint crucial reparative mechanisms. 

The therapeutic value of MSCs is being explored in a variety of diseases, including immunological inflammatory and degenerative diseases as well as cancer. Despite some setbacks, MSCs have emerged as one of the most promising sources for cell-based cardiac regenerative and reparative therapy. At present, there is a need to discern the characteristics of tissue-specific MSCs and harmonize the methods and definitions for these cells. Likewise, novel approaches (genetic engineering and tissue engineering) have been developed to enhance the use of MSCs in the treatment of various diseases. 

This Special Issue will focus on different aspects of human mesenchymal stem cells, including their molecular and functional signatures, genetic and tissue engineering to enhance their therapeutic applications. We welcome original reviews, research articles, communications, and technical notes on human mesenchymal stem cells. 

Dr. Michela Noseda
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mesenchymal stem cells
  • disease
  • cardiac
  • therapy

Published Papers (5 papers)

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Research

26 pages, 10796 KiB  
Article
HLA-Homozygous iPSC-Derived Mesenchymal Stem Cells Rescue Rotenone-Induced Experimental Leber’s Hereditary Optic Neuropathy-like Models In Vitro and In Vivo
by En-Tung Tsai, Shih-Yuan Peng, You-Ren Wu, Tai-Chi Lin, Chih-Ying Chen, Yu-Hao Liu, Yu-Hsin Tseng, Yu-Jer Hsiao, Huan-Chin Tseng, Wei-Yi Lai, Yi-Ying Lin, Yi-Ping Yang, Shih-Hwa Chiou, Shih-Pin Chen and Yueh Chien
Cells 2023, 12(22), 2617; https://doi.org/10.3390/cells12222617 - 13 Nov 2023
Viewed by 1604
Abstract
Background: Mesenchymal stem cells (MSCs) hold promise for cell-based therapy, yet the sourcing, quality, and invasive methods of MSCs impede their mass production and quality control. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) can be infinitely expanded, providing advantages over conventional MSCs in [...] Read more.
Background: Mesenchymal stem cells (MSCs) hold promise for cell-based therapy, yet the sourcing, quality, and invasive methods of MSCs impede their mass production and quality control. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) can be infinitely expanded, providing advantages over conventional MSCs in terms of meeting unmet clinical demands. Methods: The potential of MSC therapy for Leber’s hereditary optic neuropathy (LHON) remains uncertain. In this study, we used HLA-homozygous induced pluripotent stem cells to generate iMSCs using a defined protocol, and we examined their therapeutic potential in rotenone-induced LHON-like models in vitro and in vivo. Results: The iMSCs did not cause any tumorigenic incidence or inflammation-related lesions after intravitreal transplantation, and they remained viable for at least nine days in the mouse recipient’s eyes. In addition, iMSCs exhibited significant efficacy in safeguarding retinal ganglion cells (RGCs) from rotenone-induced cytotoxicity in vitro, and they ameliorated CGL+IPL layer thinning and RGC loss in vivo. Optical coherence tomography (OCT) and an electroretinogram demonstrated that iMSCs not only prevented RGC loss and impairments to the retinal architecture, but they also improved retinal electrophysiology performance. Conclusion: The generation of iMSCs via the HLA homozygosity of iPSCs offers a compelling avenue for overcoming the current limitations of MSC-based therapies. The results underscore the potential of iMSCs when addressing retinal disorders, and they highlight their clinical significance, offering renewed hope for individuals affected by LHON and other inherited retinal conditions. Full article
(This article belongs to the Special Issue Study on Human Mesenchymal Stem Cells)
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17 pages, 4191 KiB  
Article
Comparative Analysis of Biological Signatures between Freshly Preserved and Cryo-Preserved Bone Marrow Mesenchymal Stem Cells
by Taesic Lee, Sangwon Hwang, Dongmin Seo, Sungyoon Cho, Sunja Yang, Hyunsoo Kim, Jangyoung Kim and Young Uh
Cells 2023, 12(19), 2355; https://doi.org/10.3390/cells12192355 - 26 Sep 2023
Cited by 1 | Viewed by 1065
Abstract
Mesenchymal stem cells (MSCs) can differentiate into multiple connective tissue lineages, including osteoblasts, chondrocytes, and adipocytes. MSCs secrete paracrine molecules that are associated with immunomodulation, anti-fibrotic effects, and angiogenesis. Due to their orchestrative potential, MSCs have been therapeutically applied for several diseases. An [...] Read more.
Mesenchymal stem cells (MSCs) can differentiate into multiple connective tissue lineages, including osteoblasts, chondrocytes, and adipocytes. MSCs secrete paracrine molecules that are associated with immunomodulation, anti-fibrotic effects, and angiogenesis. Due to their orchestrative potential, MSCs have been therapeutically applied for several diseases. An important aspect of this process is the delivery of high-quality MSCs to patients at the right time, and cryo-biology and cryo-preservation facilitate the advancement of the logistics thereof. This study aimed to compare the biological signatures between freshly preserved and cryo-preserved MSCs by using big data sourced from the Pharmicell database. From 2011 to 2022, data on approximately 2300 stem cell manufacturing cases were collected. The dataset included approximately 60 variables, including viability, population doubling time (PDT), immunophenotype, and soluble paracrine molecules. In the dataset, 671 cases with no missing data were able to receive approval from an Institutional Review Board and were analyzed. Among the 60 features included in the final dataset, 20 were selected by experts and abstracted into two features by using a principal component analysis. Circular clustering did not introduce any differences between the two MSC preservation methods. This pattern was also observed when using viability, cluster of differentiation (CD) markers, and paracrine molecular indices as inputs for unsupervised analysis. The individual average PDT and cell viability at most passages did not differ according to the preservation method. Most immunophenotypes (except for the CD14 marker) and paracrine molecules did not exhibit different mean levels or concentrations between the frozen and unfrozen MSC groups. Collectively, the biochemical signatures of the cryo-preserved and unfrozen bone marrow MSCs were comparable. Full article
(This article belongs to the Special Issue Study on Human Mesenchymal Stem Cells)
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36 pages, 15322 KiB  
Article
Administration of Secretome Derived from Human Mesenchymal Stem Cells Induces Hepatoprotective Effects in Models of Idiosyncratic Drug-Induced Liver Injury Caused by Amiodarone or Tamoxifen
by Ya-Lin Huang, Cristian De Gregorio, Verónica Silva, Álvaro A. Elorza, Patricio Léniz, Víctor Aliaga-Tobar, Vinicius Maracaja-Coutinho, Mauricio Budini, Fernando Ezquer and Marcelo Ezquer
Cells 2023, 12(4), 636; https://doi.org/10.3390/cells12040636 - 16 Feb 2023
Cited by 5 | Viewed by 2166
Abstract
Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has [...] Read more.
Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has been shown to have hepatoprotective effects in diverse in vitro and in vivo models. In this study, we evaluate whether MSC secretome could improve DILI mediated by amiodarone (AMI) or tamoxifen (TMX). Hepatic HepG2 and HepaRG cells were incubated with AMI or TMX, alone or with the secretome of MSCs obtained from human adipose tissue. These studies demonstrate that coincubation of AMI or TMX with MSC secretome increases cell viability, prevents the activation of apoptosis pathways, and stimulates the expression of priming phase genes, leading to higher proliferation rates. As proof of concept, in a C57BL/6 mouse model of hepatic steatosis and chronic exposure to AMI, the MSC secretome was administered endovenously. In this study, liver injury was significantly attenuated, with a decrease in cell infiltration and stimulation of the regenerative response. The present results indicate that MSC secretome administration has the potential to be an adjunctive cell-free therapy to prevent liver failure derived from DILI caused by TMX or AMI. Full article
(This article belongs to the Special Issue Study on Human Mesenchymal Stem Cells)
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16 pages, 4733 KiB  
Article
Anti-Inflammatory Effect of Specialized Proresolving Lipid Mediators on Mesenchymal Stem Cells: An In Vitro Study
by Shahd AlZahrani, Zakia Shinwari, Ameera Gaafar, Ayodele Alaiya and Ahmed Al-Kahtani
Cells 2023, 12(1), 122; https://doi.org/10.3390/cells12010122 - 28 Dec 2022
Cited by 5 | Viewed by 2285
Abstract
An interconnection between tissue inflammation and regeneration has been established through the regulation of defense and repair mechanisms within diseased dental tissue triggered by the release of immune-resolvent mediators. To better our understanding of the role of specific pro-resolving mediators (SPMs) in inflamed [...] Read more.
An interconnection between tissue inflammation and regeneration has been established through the regulation of defense and repair mechanisms within diseased dental tissue triggered by the release of immune-resolvent mediators. To better our understanding of the role of specific pro-resolving mediators (SPMs) in inflamed human bone marrow-derived mesenchymal stem cells (hBMMSCs), we studied the effects of Resolvin E1 (RvE1) and Maresin 1 (MaR1) in lipopoly-saccharide (LPS) stimulated hBMMSCs. The hBMMSCs were divided into five different groups, each of which was treated with or without SPMs. Group-1: negative control (no LPS stimulation), Group-2: positive control (LPS-stimulated), Group-3: RvE1 100 nM + 1 μg/mL LPS, Group-4: MaR1 100 nM + 1 µg/mL LPS, and Group-5: RvE1 100 nM + MaR1100 nM + 1 μg/mL LPS. Cell proliferation, apoptosis, migration, colony formation, Western blotting, cytokine array, and LC/MS analysis were all performed on each group to determine the impact of SPMs on inflammatory stem cells. According to our data, RvE1 plus MaR1 effectively reduced inflammation in hBMMSCs. In particular, IL-4, 1L-10, and TGF-β1 activation and downregulation of RANKL, TNF-α, and IFN-γ compared to groups receiving single SPM were shown to be significantly different (Group 3 and 4). In addition, the LC/MS analysis revealed the differentially regulated peptide’s role in immunological pathways that define the cellular state against inflammation. Inflamed hBMMSCs treated with a combination of Resolvin E1 (RvE1) and Maresin 1 (MaR1) promoted the highest inflammatory resolution compared to the other groups; this finding suggests a potential new approach of treating bacterially induced dental infections. Full article
(This article belongs to the Special Issue Study on Human Mesenchymal Stem Cells)
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19 pages, 4656 KiB  
Article
Exosomes from Human Omental Adipose-Derived Mesenchymal Stem Cells Secreted into Ascites Promote Peritoneal Metastasis of Epithelial Ovarian Cancer
by Qingxi Qu, Linghong Liu, Yuqian Cui, Yu Chen, Yu Wang and Yaodu Wang
Cells 2022, 11(21), 3392; https://doi.org/10.3390/cells11213392 - 27 Oct 2022
Cited by 8 | Viewed by 2212
Abstract
Epithelial ovarian cancer (EOC) patients frequently develop peritoneal metastasis, especially in the human omentum. However, the mechanism underlying this propensity remains unknown. A previous study found that human omental adipose-derived mesenchymal stem cells are potentially involved in ovarian cancer growth and metastasis, but [...] Read more.
Epithelial ovarian cancer (EOC) patients frequently develop peritoneal metastasis, especially in the human omentum. However, the mechanism underlying this propensity remains unknown. A previous study found that human omental adipose-derived mesenchymal stem cells are potentially involved in ovarian cancer growth and metastasis, but the results were inconsistent and even contradictory. In addition, the underlying mechanisms of visceral adipose metastasis remain poorly understood. Here, our goal is to clarify the role and mechanism of human omental adipose-derived mesenchymal stem cells (HO-ADSCs) in EOC cancer growth and metastasis. We first found that human omental tissue conditioned medium (HO-CM) enhances EOC cell function. Subsequent coculture studies indicated that HO-ADSCs increase the growth, migratory and invasive capabilities of ovarian cancer cells. Then, we demonstrated that exosomes secreted by HO-ADSCs (HO-ADSC exosomes) enhanced ovarian cancer cell function, and further mechanistic studies showed that the FOXM1, Cyclin F, KIF20A, and MAPK signaling pathways were involved in this process. In addition, subcutaneous tumorigenesis and peritoneal metastatic xenograft experiments provided evidence that HO-ADSC exosomes promote ovarian cancer growth and metastasis in vivo. Finally, our clinical studies provided evidence that ascites from ovarian cancer patients enhance EOC cell line proliferation, migration, and invasion in vitro. The present study indicated that HO-ADSC exosomes are secreted into ascites and exert a tumor-promoting effect on EOC growth and metastasis, providing a new perspective and method to develop future novel therapeutic strategies for the treatment of ovarian cancer. Full article
(This article belongs to the Special Issue Study on Human Mesenchymal Stem Cells)
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