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Molecular Research in Human Stem Cells
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Molecular Research in Human Stem Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 December 2024 | Viewed by 4474

Special Issue Editors

Dr. Carmen Ciavarella

E-Mail Website
Guest Editor
Laboratory of Clinical Pathology, Department of Medical and Surgical Sciences (DIMEC), S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
Interests: mesenchymal stem cells; cardiovascular disease; atherosclerosis; microRNA; cell differentiation; endothelial to mesenchymal transition (End-MT); inflammation; PPAR-γ
Dr. Sabrina Valente

E-Mail Website
Guest Editor
Department of Medical and Surgical Sciences—DIMEC, University of Bologna, 40138 Bologna, Italy
Interests: mesenchymal stem cells; in vitro 3D models; electron microscopy; cell-biomaterial interactions; extracellular vescicles; vascular diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stem cells constitute a reservoir of pluripotent cells, capable of differentiating into multiple specialized cell types, and meanwhile, they are endowed with self-renewal to continue the stem cell niche. The stem cell differentiation process is tightly regulated at several levels, like the chemokine/growth factor amount within the microenvironment and the molecular switchers. In this category, transcription factors, signal transduction pathways, microRNA (miRNA) and epigenetics (i.e., DNA methylation, acetylation, phosphorylation) are critical fine tuners of stem cell behavior and phenotypes, including the malignant fate. Therefore, investigating the main mechanisms that govern stem cell biology and fate decision would be promising for translational purposes, bridging the gap between the therapeutic potential and the involvement of stem cells in human disease.

This Special Issue of IJMS will cover the molecular regulatory mechanisms that shape stem cell properties and phenotypes, including in the pathological setting. Biomolecular experiments exploring the transcriptional switchers and miRNAs in stem cell biology are welcome.

Dr. Carmen Ciavarella
Dr. Sabrina Valente
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • stem cells
  • mesenchymal stem cells
  • miRNA
  • differentiation
  • self-renewal
  • inflammation
  • transcription factors
  • senescence
  • extracellular vesicles

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Published Papers (5 papers)

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Research

17 pages, 5997 KiB  
Article
PTH1R Suppressed Apoptosis of Mesenchymal Progenitors in Mandibular Growth
by Chen Cui, Chuang Lu, Yanling Cai, Yuhua Xiong, Yihong Duan, Kaiwen Lan, Yi Fan, Xuedong Zhou and Xi Wei
Int. J. Mol. Sci. 2024, 25(23), 12607; https://doi.org/10.3390/ijms252312607 - 24 Nov 2024
Viewed by 271
Abstract
Genetic abnormalities of the parathyroid hormone 1 receptor (PTH1R) lead to profound craniomaxillofacial bone and dentition defects on account of inappropriate tissue metabolism and cellular differentiation. The coordinated activity of differentiation and viability in bone cells is indispensable for bone metabolism. Recent research [...] Read more.
Genetic abnormalities of the parathyroid hormone 1 receptor (PTH1R) lead to profound craniomaxillofacial bone and dentition defects on account of inappropriate tissue metabolism and cellular differentiation. The coordinated activity of differentiation and viability in bone cells is indispensable for bone metabolism. Recent research demonstrates mesenchymal progenitors are responsive to PTH1R signaling for osteogenic differentiation, whereas the effect of PTH1R on cellular survival remains incompletely understood. Here, we report that mice with deletion of PTH1R in Prx1-positive mesenchymal cells (Prx1Cre;PTH1Rfl/fl) exhibit decreased alveolar bone mass due in part to apoptotic response activation. The exploration of oral bone-derived mesenchymal stem cells (OMSCs) with PTH1R deficiency suggests PTH1R signaling modulates OMSCs’ apoptosis by interfering mitochondrial function and morphology. The underlying molecular mechanisms are studied by transcriptome sequencing analysis, finding that inositol trisphosphate receptor-3 (IP3R-3), an endoplasmic reticulum calcium channel protein, serves as a modulator of pro-apoptosis in OMSCs. Furthermore, we find PTH1R and its downstream protein kinase A (PKA) pathway dampen IP3R-3’s expression. Of note, OMSCs with IP3R-3 overexpression recapitulate the PTH1R-deletion phenotypes, while IP3R-3 silence rescues mitochondrial dysfunction. Altogether, our study uncovers the anti-apoptotic function of PTH1R signaling in OMSCs and proves that excess apoptosis partly contributes to a weakening potential of osteogenic differentiation and aberrant mandibular development. Full article
(This article belongs to the Special Issue Molecular Research in Human Stem Cells)
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14 pages, 2882 KiB  
Article
Heparin Differentially Regulates the Expression of Specific miRNAs in Mesenchymal Stromal Cells
by Michaela Oeller, Tanja Schally, Georg Zimmermann, Wanda Lauth, Katharina Schallmoser, Eva Rohde and Sandra Laner-Plamberger
Int. J. Mol. Sci. 2024, 25(23), 12589; https://doi.org/10.3390/ijms252312589 - 23 Nov 2024
Viewed by 297
Abstract
In regenerative medicine, stromal cells are supposed to play an important role by modulating immune responses and differentiating into various tissue types. The aim of this study was to investigate the influence of heparin, frequently used as an anticoagulant in human platelet lysate [...] Read more.
In regenerative medicine, stromal cells are supposed to play an important role by modulating immune responses and differentiating into various tissue types. The aim of this study was to investigate the influence of heparin, frequently used as an anticoagulant in human platelet lysate (HPL)-supplemented cell cultures, on the expression of non-coding RNA species, particularly microRNAs (miRNA), which are pivotal regulators of gene expression. Through genomic analysis and quantitative RT-PCR, we assessed the differential impact of heparin on miRNA expression in various stromal cell types, derived from human bone marrow, umbilical cord and white adipose tissue. Our results demonstrate that heparin significantly alters miRNA expression, with distinct up- and downregulation patterns depending on the original tissue source of human stromal cells. Furthermore, our analyses indicate that these heparin-induced alterations in miRNA expression profiles influence critical cellular processes, including proliferation, apoptosis and differentiation. In conclusion, our study highlights that heparin not only fulfills its primary role as an efficient anticoagulant but can also modulate important regulatory pathways in stromal cells by influencing miRNA expression. This may alter cellular properties and thus influence stromal cell-based therapeutic applications in regenerative medicine. Full article
(This article belongs to the Special Issue Molecular Research in Human Stem Cells)
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13 pages, 2274 KiB  
Article
IFN-β Overexpressing Adipose-Derived Mesenchymal Stem Cells Mitigate Alcohol-Induced Liver Damage and Gut Permeability
by Soonjae Hwang, Young Woo Eom, Seong Hee Kang, Soon Koo Baik and Moon Young Kim
Int. J. Mol. Sci. 2024, 25(15), 8509; https://doi.org/10.3390/ijms25158509 - 4 Aug 2024
Viewed by 1099
Abstract
Alcoholic liver disease (ALD) is a form of hepatic inflammation. ALD is mediated by gut leakiness. This study evaluates the anti-inflammatory effects of ASCs overexpressing interferon-beta (ASC-IFN-β) on binge alcohol-induced liver injury and intestinal permeability. In vitro, ASCs were transfected with a non-viral [...] Read more.
Alcoholic liver disease (ALD) is a form of hepatic inflammation. ALD is mediated by gut leakiness. This study evaluates the anti-inflammatory effects of ASCs overexpressing interferon-beta (ASC-IFN-β) on binge alcohol-induced liver injury and intestinal permeability. In vitro, ASCs were transfected with a non-viral vector carrying the human IFN-β gene, which promoted hepatocyte growth factor (HGF) secretion in the cells. To assess the potential effects of ASC-IFN-β, C57BL/6 mice were treated with three oral doses of binge alcohol and were administered intraperitoneal injections of ASC-IFN-β. Mice treated with binge alcohol and administered ASC-IFN-β showed reduced liver injury and inflammation compared to those administered a control ASC. Analysis of intestinal tissue from ethanol-treated mice administered ASC-IFN-β also indicated decreased inflammation. Additionally, fecal albumin, blood endotoxin, and bacterial colony levels were reduced, indicating less gut leakiness in the binge alcohol-exposed mice. Treatment with HGF, but not IFN-β or TRAIL, mitigated the ethanol-induced down-regulation of cell death and permeability in Caco-2 cells. These results demonstrate that ASCs transfected with a non-viral vector to induce IFN-β overexpression have protective effects against binge alcohol-mediated liver injury and gut leakiness via HGF. Full article
(This article belongs to the Special Issue Molecular Research in Human Stem Cells)
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15 pages, 10966 KiB  
Article
Amelioration of Photoreceptor Degeneration by Intravitreal Transplantation of Retinal Progenitor Cells in Rats
by Jing Yang, Geoffrey P. Lewis, Chin-Hui Hsiang, Steven Menges, Gabriel Luna, William Cho, Nikolay Turovets, Steven K. Fisher and Henry Klassen
Int. J. Mol. Sci. 2024, 25(15), 8060; https://doi.org/10.3390/ijms25158060 - 24 Jul 2024
Viewed by 966
Abstract
Photoreceptor degeneration is a major cause of untreatable blindness worldwide and has recently been targeted by emerging technologies, including cell- and gene-based therapies. Cell types of neural lineage have shown promise for replacing either photoreceptors or retinal pigment epithelial cells following delivery to [...] Read more.
Photoreceptor degeneration is a major cause of untreatable blindness worldwide and has recently been targeted by emerging technologies, including cell- and gene-based therapies. Cell types of neural lineage have shown promise for replacing either photoreceptors or retinal pigment epithelial cells following delivery to the subretinal space, while cells of bone marrow lineage have been tested for retinal trophic effects following delivery to the vitreous cavity. Here we explore an alternate approach in which cells from the immature neural retinal are delivered to the vitreous cavity with the goal of providing trophic support for degenerating photoreceptors. Rat and human retinal progenitor cells were transplanted to the vitreous of rats with a well-studied photoreceptor dystrophy, resulting in substantial anatomical preservation and functional rescue of vision. This work provides scientific proof-of-principle for a novel therapeutic approach to photoreceptor degeneration that is currently being evaluated in clinical trials. Full article
(This article belongs to the Special Issue Molecular Research in Human Stem Cells)
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17 pages, 12385 KiB  
Article
Mesenchymal Stem Cells from Mouse Hair Follicles Inhibit the Development of Type 1 Diabetes
by Dragica Mićanović, Suzana Stanisavljević, Hanluo Li, Ivan Koprivica, Natalija Jonić, Ivana Stojanović, Vuk Savković and Tamara Saksida
Int. J. Mol. Sci. 2024, 25(11), 5974; https://doi.org/10.3390/ijms25115974 - 29 May 2024
Viewed by 1288
Abstract
Mesenchymal stem cells (MSCs) are known for their immunosuppressive properties. Based on the demonstrated anti-inflammatory effect of mouse MSCs from hair follicles (moMSCORS) in a murine wound closure model, this study evaluates their potential for preventing type 1 diabetes (T1D) in C57BL/6 mice. [...] Read more.
Mesenchymal stem cells (MSCs) are known for their immunosuppressive properties. Based on the demonstrated anti-inflammatory effect of mouse MSCs from hair follicles (moMSCORS) in a murine wound closure model, this study evaluates their potential for preventing type 1 diabetes (T1D) in C57BL/6 mice. T1D was induced in C57BL/6 mice by repeated low doses of streptozotocin. moMSCORS were injected intravenously on weekly basis. moMSCORS reduced T1D incidence, the insulitis stage, and preserved insulin production in treated animals. moMSCORS primarily exerted immunomodulatory effects by inhibiting CD4+ T cell proliferation and activation. Ex vivo analysis indicated that moMSCORS modified the cellular immune profile within pancreatic lymph nodes and pancreatic infiltrates by reducing the numbers of M1 pro-inflammatory macrophages and T helper 17 cells and upscaling the immunosuppressive T regulatory cells. The proportion of pathogenic insulin-specific CD4+ T cells was down-scaled in the lymph nodes, likely via soluble factors. The moMSCORS detected in the pancreatic infiltrates of treated mice presumably exerted the observed suppressive effect on CD4+ through direct contact. moMSCORS alleviated T1D symptoms in the mouse, qualifying as a candidate for therapeutic products by multiple advantages: non-invasive sampling by epilation, easy access, permanent availability, scalability, and benefits of auto-transplantation. Full article
(This article belongs to the Special Issue Molecular Research in Human Stem Cells)
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