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Cells
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Microenvironmental Factors and Functional Modulation in Mesenchymal Stem Cells 2.0
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Microenvironmental Factors and Functional Modulation in Mesenchymal Stem Cells 2.0

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

Deadline for manuscript submissions: 31 January 2025 | Viewed by 7137

Special Issue Editors

Dr. Mohamed Mekhemar

E-Mail Website
Guest Editor
Clinic for Conservative Dentistry and Periodontology, University of Kiel, 24105 Kiel, Germany
Interests: periodontology; stem cells; regeneration; oral health
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Karim Mohamed Fawzy El-Sayed

E-Mail
Guest Editor
1. Clinic for Conservative Dentistry and Periodontology, University of Kiel, 24105 Kiel, Germany
2. Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt
Interests: periodontal regeneration; progenitor cells; dentistry; stem cell biology

Special Issue Information

Dear Colleagues,

Mesenchymal stem cells (MSCs) are biological candidates for numerous applications in the fields of regenerative medicine and immunotherapy. Their multilineage differentiation ability and immune modulatory functions promote their application for disease management in different inflammatory, degenerative, and immunological conditions. However, the local cellular microenvironment and the MSC source can control miscellaneous biological features of these cells. The crosstalk between mesenchymal stem cells and numerous microenvironmental factors has been reported to endorse a variety of biological responses and functions. Stimulation or inhibition of MSC receptors and functions by the surrounding microenvironmental factors before or within potential treatment events may serve as an effective method to control the biological function of MSCs as needed in different therapeutic stages of the disease.

This Special Issue aims to be a collection of recent research on microenvironmental factors and functional modulation in mesenchymal stem cells.

We look forward to your contributions.

Dr. Mohamed Mekhemar
Prof. Dr. Karim Mohamed Fawzy El-Sayed
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. 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
  • inflammation
  • microenvironment
  • regeneration of mesenchymal stem cell receptors
  • stem cell differentiation

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Related Special Issue

Published Papers (5 papers)

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Research

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13 pages, 1960 KiB  
Article
PDGF-BB Deficiency in the Blood Serum from Aplastic Anemia Patients Affects Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells
by Alena I. Dorofeeva, Irina N. Shipounova, Ksenia A. Nikiforova, Irina V. Galtseva, Larisa A. Kuzmina, Anton V. Luchkin, Zalina T. Fidarova, Elena A. Mikhailova and Elena N. Parovichnikova
Cells 2024, 13(22), 1908; https://doi.org/10.3390/cells13221908 - 18 Nov 2024
Viewed by 309
Abstract
Aplastic anemia (AA) is characterized by bone marrow (BM) aplasia and pancytopenia. BM stromal microenvironment is closely intertwined with hematopoietic cells by reciprocal regulation. It is still unclear how hematopoietic deficiency affects the bone marrow stroma of the AA patients. Multipotent mesenchymal stromal [...] Read more.
Aplastic anemia (AA) is characterized by bone marrow (BM) aplasia and pancytopenia. BM stromal microenvironment is closely intertwined with hematopoietic cells by reciprocal regulation. It is still unclear how hematopoietic deficiency affects the bone marrow stroma of the AA patients. Multipotent mesenchymal stromal cells (MMSCs) are the progenitors of stromal cells. In vitro, proliferation rate of MMSCs of AA patients is decreased compared to those of healthy donors. This may be explained by the influence of pathological environmental condition in the patients’ BM. The aim of the study was to compare the effect of AA patients’ sera on healthy donor MMSCs to healthy donors’ sera and to elucidate the nature of their difference. Proliferation test showed 3-fold decrease in number of MMSCs after incubation in medium supplemented with AA patients’ sera compared to donors’ serum samples. The degree of this effect correlated with the severity of thrombocytopenia in patients. The decrease in cell number was not associated with cell death, as the number of apoptotic cells defined by flow cytometry did not differ between the groups. ELISA revealed a decreased level of PDGF-BB in the patients’ sera compared to donors’ serum samples (69 ± 5 pg/mL vs. 112 ± 21 pg/mL, respectively). The addition of recombinant PDGF-BB or healthy donor’s platelet lysate to the culture medium supplemented with AA patients’ serum restored its ability to support MMSCs growth. Thus, PDGF-BB deficiency is one of the environmental factors causing MMSCs damage in AA patients. Full article
(This article belongs to the Special Issue Microenvironmental Factors and Functional Modulation in Mesenchymal Stem Cells 2.0)
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17 pages, 3410 KiB  
Article
The Effects of the Pneumonia Lung Microenvironment on MSC Function
by Lanzhi Liu, Juan Fandiño, Sean D. McCarthy, Claire H. Masterson, Ignacio Sallent, Shanshan Du, Abigail Warren, John G. Laffey and Daniel O’Toole
Cells 2024, 13(18), 1581; https://doi.org/10.3390/cells13181581 - 20 Sep 2024
Viewed by 712
Abstract
Background: Despite promise in preclinical models of acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC) have failed to translate to therapeutic benefit in clinical trials. The MSC is a live cell medicine and interacts with the patient’s disease state. Here, we explored [...] Read more.
Background: Despite promise in preclinical models of acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC) have failed to translate to therapeutic benefit in clinical trials. The MSC is a live cell medicine and interacts with the patient’s disease state. Here, we explored this interaction, seeking to devise strategies to enhance MSC therapeutic function. Methods: Human bone-marrow-derived MSCs were exposed to lung homogenate from healthy and E. coli-induced ARDS rat models. Apoptosis and functional assays of the MSCs were performed. Results: The ARDS model showed reduced arterial oxygenation, decreased lung compliance and an inflammatory microenvironment compared to controls. MSCs underwent more apoptosis after stimulation by lung homogenate from controls compared to E. coli, which may explain why MSCs persist longer in ARDS subjects after administration. Changes in expression of cell surface markers and cytokines were associated with lung homogenate from different groups. The anti-microbial effects of MSCs did not change with the stimulation. Moreover, the conditioned media from lung-homogenate-stimulated MSCs inhibited T-cell proliferation. Conclusions: These findings suggest that the ARDS microenvironment plays an important role in the MSC’s therapeutic mechanism of action, and changes can inform strategies to modulate MSC-based cell therapy for ARDS. Full article
(This article belongs to the Special Issue Microenvironmental Factors and Functional Modulation in Mesenchymal Stem Cells 2.0)
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20 pages, 14544 KiB  
Article
Administration of Human-Derived Mesenchymal Stem Cells Activates Locally Stimulated Endogenous Neural Progenitors and Reduces Neurological Dysfunction in Mice after Ischemic Stroke
by Shuichi Fujiwara, Akiko Nakano-Doi, Toshinori Sawano, Shuji Kubo, Nobutaka Doe and Takayuki Nakagomi
Cells 2024, 13(11), 939; https://doi.org/10.3390/cells13110939 - 29 May 2024
Viewed by 979
Abstract
Increasing evidence shows that the administration of mesenchymal stem cells (MSCs) is a promising option for various brain diseases, including ischemic stroke. Studies have demonstrated that MSC transplantation after ischemic stroke provides beneficial effects, such as neural regeneration, partially by activating endogenous neural [...] Read more.
Increasing evidence shows that the administration of mesenchymal stem cells (MSCs) is a promising option for various brain diseases, including ischemic stroke. Studies have demonstrated that MSC transplantation after ischemic stroke provides beneficial effects, such as neural regeneration, partially by activating endogenous neural stem/progenitor cells (NSPCs) in conventional neurogenic zones, such as the subventricular and subgranular zones. However, whether MSC transplantation regulates the fate of injury-induced NSPCs (iNSPCs) regionally activated at injured regions after ischemic stroke remains unclear. Therefore, mice were subjected to ischemic stroke, and mCherry-labeled human MSCs (h-MSCs) were transplanted around the injured sites of nestin–GFP transgenic mice. Immunohistochemistry of brain sections revealed that many GFP+ cells were observed around the grafted sites rather than in the regions in the subventricular zone, suggesting that transplanted mCherry+ h-MSCs stimulated GFP+ locally activated endogenous iNSPCs. In support of these findings, coculture studies have shown that h-MSCs promoted the proliferation and neural differentiation of iNSPCs extracted from ischemic areas. Furthermore, pathway analysis and gene ontology analysis using microarray data showed that the expression patterns of various genes related to self-renewal, neural differentiation, and synapse formation were changed in iNSPCs cocultured with h-MSCs. We also transplanted h-MSCs (5.0 × 104 cells/µL) transcranially into post-stroke mouse brains 6 weeks after middle cerebral artery occlusion. Compared with phosphate-buffered saline-injected controls, h-MSC transplantation displayed significantly improved neurological functions. These results suggest that h-MSC transplantation improves neurological function after ischemic stroke in part by regulating the fate of iNSPCs. Full article
(This article belongs to the Special Issue Microenvironmental Factors and Functional Modulation in Mesenchymal Stem Cells 2.0)
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16 pages, 3627 KiB  
Article
Effect of Hyperbaric Oxygen and Inflammation on Human Gingival Mesenchymal Stem/Progenitor Cells
by Johannes Tölle, Andreas Koch, Kristina Schlicht, Dirk Finger, Wataru Kaehler, Marc Höppner, Christian Graetz, Christof Dörfer, Dominik M. Schulte and Karim Fawzy El-Sayed
Cells 2023, 12(20), 2479; https://doi.org/10.3390/cells12202479 - 18 Oct 2023
Cited by 1 | Viewed by 1669
Abstract
The present study explores for the first time the effect of hyperbaric oxygen (HBO) on gingival mesenchymal stem cells’ (G-MSCs) gene expression profile, intracellular pathway activation, pluripotency, and differentiation potential under an experimental inflammatory setup. G-MSCs were isolated from five healthy individuals ( [...] Read more.
The present study explores for the first time the effect of hyperbaric oxygen (HBO) on gingival mesenchymal stem cells’ (G-MSCs) gene expression profile, intracellular pathway activation, pluripotency, and differentiation potential under an experimental inflammatory setup. G-MSCs were isolated from five healthy individuals (n = 5) and characterized. Single (24 h) or double (72 h) HBO stimulation (100% O2, 3 bar, 90 min) was performed under experimental inflammatory [IL-1β (1 ng/mL)/TNF-α (10 ng/mL)/IFN-γ (100 ng/mL)] and non-inflammatory micro-environment. Next Generation Sequencing and KEGG pathway enrichment analysis, G-MSCs’ pluripotency gene expression, Wnt-/β-catenin pathway activation, proliferation, colony formation, and differentiation were investigated. G-MSCs demonstrated all mesenchymal stem/progenitor cells’ characteristics. The beneficial effect of a single HBO stimulation was evident, with anti-inflammatory effects and induction of differentiation (TLL1, ID3, BHLHE40), proliferation/cell survival (BMF, ID3, TXNIP, PDK4, ABL2), migration (ABL2) and osteogenic differentiation (p < 0.05). A second HBO stimulation at 72 h had a detrimental effect, significantly increasing the inflammation-induced cellular stress and ROS accumulation through HMOX1, BHLHE40, and ARL4C amplification and pathway enrichment (p < 0.05). Results outline a positive short-term single HBO anti-inflammatory, regenerative, and differentiation stimulatory effect on G-MSCs. A second (72 h) stimulation is detrimental to the same properties. The current results could open new perspectives in the clinical application of short-termed HBO induction in G-MSCs-mediated periodontal reparative/regenerative mechanisms. Full article
(This article belongs to the Special Issue Microenvironmental Factors and Functional Modulation in Mesenchymal Stem Cells 2.0)
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Review

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38 pages, 4189 KiB  
Review
PTH and the Regulation of Mesenchymal Cells within the Bone Marrow Niche
by Hanghang Liu, Linyi Liu and Clifford J. Rosen
Cells 2024, 13(5), 406; https://doi.org/10.3390/cells13050406 - 26 Feb 2024
Cited by 6 | Viewed by 2951
Abstract
Parathyroid hormone (PTH) plays a pivotal role in maintaining calcium homeostasis, largely by modulating bone remodeling processes. Its effects on bone are notably dependent on the duration and frequency of exposure. Specifically, PTH can initiate both bone formation and resorption, with the outcome [...] Read more.
Parathyroid hormone (PTH) plays a pivotal role in maintaining calcium homeostasis, largely by modulating bone remodeling processes. Its effects on bone are notably dependent on the duration and frequency of exposure. Specifically, PTH can initiate both bone formation and resorption, with the outcome being influenced by the manner of PTH administration: continuous or intermittent. In continuous administration, PTH tends to promote bone resorption, possibly by regulating certain genes within bone cells. Conversely, intermittent exposure generally favors bone formation, possibly through transient gene activation. PTH’s role extends to various aspects of bone cell activity. It directly influences skeletal stem cells, osteoblastic lineage cells, osteocytes, and T cells, playing a critical role in bone generation. Simultaneously, it indirectly affects osteoclast precursor cells and osteoclasts, and has a direct impact on T cells, contributing to its role in bone resorption. Despite these insights, the intricate mechanisms through which PTH acts within the bone marrow niche are not entirely understood. This article reviews the dual roles of PTH—catabolic and anabolic—on bone cells, highlighting the cellular and molecular pathways involved in these processes. The complex interplay of these factors in bone remodeling underscores the need for further investigation to fully comprehend PTH’s multifaceted influence on bone health. Full article
(This article belongs to the Special Issue Microenvironmental Factors and Functional Modulation in Mesenchymal Stem Cells 2.0)
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