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Therapeutic Modulation of Mesenchymal Stem Cell for Effective Regenerative Medicine
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Therapeutic Modulation of Mesenchymal Stem Cell for Effective Regenerative Medicine

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: 15 May 2024 | Viewed by 8366

Special Issue Editor

Prof. Dr. Margherita Maioli

E-Mail Website
Guest Editor
Department of Biochemical Science, University of Sassari, 07100 Sassari, Italy
Interests: stem cells; cell senescence; stem cell differentiation; adipogenesis; osteogenesis; cardiogenesis; conditioned media; nutraceuticals; gene expression; epigenetics; cellular mechanisms; cell-based therapies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mesenchymal stem cells (MSCs) are multipotent stem cells derived from the mesenchyme. MSCs are able to self-renew and differentiate into different lineages as adipose, skeletal, and connective tissues. The main role of adult resident MSCs is to maintain cellular tissue homeostasis. MSCs are considered ideal candidates for tissue regeneration and tissue engineering, and interest in their biological roles is growing.

Stem cells have been widely explored in the branch of regenerative medicine, being able to replace damaged elements due to their ability to undergo a differentiation process. Based on signals released from organ-specific niches, stem cells commit to a specific cell lineage. Therefore, stem cells express lineage-specific genes, repopulating their own stem cell compartment and differentiating into the organ-specific cell population. Recent evidence suggest that bioactive molecules are able to modulate stem cell behaviour in vitro, representing an interesting tool for therapeutic application of MSCs.

This Special Issue will accept submissions in the form of original research articles, reviews, and methods on stem cell behaviour, cellular phenotype in MSC-based therapies. We aim at defining recent progress in stem cells biology in relation to their therapeutic potential, new approaches in committing stem cells toward specific phenotypes, and data from clinical trials of cell-based therapies. Moreover, the mechanisms of stem cells activity including specific biomarkers or epigenetic signatures will be presented.

Prof. Dr. Margherita Maioli
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. 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
  • cell senescence
  • stem cell differentiation
  • adipogenesis
  • osteogenesis
  • cardiogenesis
  • conditioned media
  • epigenetics
  • biomarkers
  • cell-based therapies
  • malignant transformation

Published Papers (5 papers)

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Research

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14 pages, 886 KiB  
Article
Effect of Helichrysum italicum in Promoting Collagen Deposition and Skin Regeneration in a New Dynamic Model of Skin Wound Healing
by Diletta Serra, Sara Cruciani, Giuseppe Garroni, Giorgia Sarais, Fikriye Fulya Kavak, Rosanna Satta, Maria Antonietta Montesu, Matteo Floris, Carlo Ventura and Margherita Maioli
Int. J. Mol. Sci. 2024, 25(9), 4736; https://doi.org/10.3390/ijms25094736 - 26 Apr 2024
Viewed by 151
Abstract
Natural products have many healing effects on the skin with minimal or no adverse effects. In this study, we analyzed the regenerative properties of a waste product (hydrolate) derived from Helichrysum italicum (HH) on scratch-tested skin cell populations seeded on a [...] Read more.
Natural products have many healing effects on the skin with minimal or no adverse effects. In this study, we analyzed the regenerative properties of a waste product (hydrolate) derived from Helichrysum italicum (HH) on scratch-tested skin cell populations seeded on a fluidic culture system. Helichrysum italicum has always been recognized in the traditional medicine of Mediterranean countries for its wide pharmacological activities. We recreated skin physiology with a bioreactor that mimics skin stem cell (SSCs) and fibroblast (HFF1) communication as in vivo skin layers. Dynamic culture models represent an essential instrument for recreating and preserving the complex multicellular organization and interactions of the cellular microenvironment. Both cell types were exposed to two different concentrations of HH after the scratch assay and were compared to untreated control cells. Collagen is the constituent of many wound care products that act directly on the damaged wound environment. We analyzed the role played by HH in stimulating collagen production during tissue repair, both in static and dynamic culture conditions, by a confocal microscopic analysis. In addition, we performed a gene expression analysis that revealed the activation of a molecular program of stemness in treated skin stem cells. Altogether, our results indicate a future translational application of this natural extract to support skin regeneration and define a new protocol to recreate a dynamic process of healing. Full article
(This article belongs to the Special Issue Therapeutic Modulation of Mesenchymal Stem Cell for Effective Regenerative Medicine)
16 pages, 3372 KiB  
Article
Plasma Small Extracellular Vesicle Cardiac miRNA Expression in Patients with Ischemic Heart Failure, Randomized to Percutaneous Intramyocardial Treatment of Adipose Derived Stem Cells or Placebo: Subanalysis of the SCIENCE Study
by Denise Traxler, Varius Dannenberg, Katrin Zlabinger, Alfred Gugerell, Julia Mester-Tonczar, Dominika Lukovic, Andreas Spannbauer, Ena Hasimbegovic, Jens Kastrup and Mariann Gyöngyösi
Int. J. Mol. Sci. 2023, 24(13), 10647; https://doi.org/10.3390/ijms241310647 - 26 Jun 2023
Cited by 1 | Viewed by 1102
Abstract
Small extracellular vesicles (EVs) and their cargo are an important component of cell-to-cell communication in cardiac disease. Allogeneic adipose derived stem cells (ADSCs) are thought to be a potential approach for cardiac regenerative therapy in ischemic heart disease. The SCIENCE study investigated the [...] Read more.
Small extracellular vesicles (EVs) and their cargo are an important component of cell-to-cell communication in cardiac disease. Allogeneic adipose derived stem cells (ADSCs) are thought to be a potential approach for cardiac regenerative therapy in ischemic heart disease. The SCIENCE study investigated the effect of ADSCs administered via intramyocardial injection on cardiac function in patients with ischemic heart disease. The aim of this substudy, based on samples from 15 patients, was to explore small EV miRNA dynamics after treatment with ADSCs compared to a placebo. Small EVs were isolated at several timepoints after the percutaneous intramyocardial application of ADSCs. No significant effect of ADSC treatment on small EV concentration was detected. After 12 months, the expression of miR-126 decreased significantly in ADSC patients, but not in the placebo-treated group. However, all cardiac miRNAs correlated with plasma cardiac biomarkers. In line with the overall negative results of the SCIENCE study, with the exception of one miR, we did not detect any significant regulation of small EV miRNAs in this patient collective. Full article
(This article belongs to the Special Issue Therapeutic Modulation of Mesenchymal Stem Cell for Effective Regenerative Medicine)
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15 pages, 2392 KiB  
Article
Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma
by Hye-Rim Seong, Chan Ho Noh, Sangryong Park, Sumin Cho, Seok-Jin Hong, Ah-young Lee, Dongho Geum, Soon-Cheol Hong, Dongsun Park, Tae Myoung Kim, Ehn-Kyoung Choi and Yun-Bae Kim
Int. J. Mol. Sci. 2023, 24(9), 8073; https://doi.org/10.3390/ijms24098073 - 29 Apr 2023
Cited by 5 | Viewed by 1912
Abstract
Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important [...] Read more.
Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O2) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O2) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H2O2-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H2O2- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12–17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9–4.5 × 108 exosomes in 10 μL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 μg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma. Full article
(This article belongs to the Special Issue Therapeutic Modulation of Mesenchymal Stem Cell for Effective Regenerative Medicine)
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Review

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31 pages, 1637 KiB  
Review
Mesenchymal Stem Cell Therapy in Traumatic Spinal Cord Injury: A Systematic Review
by Rodrigo Montoto-Meijide, Rosa Meijide-Faílde, Silvia María Díaz-Prado and Antonio Montoto-Marqués
Int. J. Mol. Sci. 2023, 24(14), 11719; https://doi.org/10.3390/ijms241411719 - 20 Jul 2023
Cited by 4 | Viewed by 2746
Abstract
Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. Cell therapy, particularly with mesenchymal stem cells (MSCs), holds significant promise for TSCI treatment. This [...] Read more.
Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. Cell therapy, particularly with mesenchymal stem cells (MSCs), holds significant promise for TSCI treatment. This systematic review aims to analyze the efficacy, safety, and therapeutic potential of MSC-based cell therapies in TSCI. A comprehensive search of PUBMED and COCHRANE databases until February 2023 was conducted, combining terms such as “spinal cord injury,” “stem cells,” “stem cell therapy,” “mesenchymal stem cells,” and “traumatic spinal cord injury”. Among the 53 studies initially identified, 22 (21 clinical trials and 1 case series) were included. Findings from these studies consistently demonstrate improvements in AIS (ASIA Impairment Scale) grades, sensory scores, and, to a lesser extent, motor scores. Meta-analyses further support these positive outcomes. MSC-based therapies have shown short- and medium-term safety, as indicated by the absence of significant adverse events within the studied timeframe. However, caution is required when drawing generalized recommendations due to the limited scientific evidence available. Further research is needed to elucidate the long-term safety and clinical implications of these advancements. Although significant progress has been made, particularly with MSC-based therapies, additional studies exploring other potential future therapies such as gene therapies, neurostimulation techniques, and tissue engineering approaches are essential for a comprehensive understanding of the evolving TSCI treatment landscape. Full article
(This article belongs to the Special Issue Therapeutic Modulation of Mesenchymal Stem Cell for Effective Regenerative Medicine)
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49 pages, 16914 KiB  
Review
Signal Pathways and microRNAs in Osteosarcoma Growth and the Dual Role of Mesenchymal Stem Cells in Oncogenesis
by Natalia Todosenko, Igor Khlusov, Kristina Yurova, Olga Khaziakhmatova and Larisa Litvinova
Int. J. Mol. Sci. 2023, 24(10), 8993; https://doi.org/10.3390/ijms24108993 - 19 May 2023
Cited by 4 | Viewed by 1756
Abstract
The major challenges in Osteosarcoma (OS) therapy are its heterogeneity and drug resistance. The development of new therapeutic approaches to overcome the major growth mechanisms of OS is urgently needed. The search for specific molecular targets and promising innovative approaches in OS therapy, [...] Read more.
The major challenges in Osteosarcoma (OS) therapy are its heterogeneity and drug resistance. The development of new therapeutic approaches to overcome the major growth mechanisms of OS is urgently needed. The search for specific molecular targets and promising innovative approaches in OS therapy, including drug delivery methods, is an urgent problem. Modern regenerative medicine focuses on harnessing the potential of mesenchymal stem cells (MSCs) because they have low immunogenicity. MSCs are important cells that have received considerable attention in cancer research. Currently, new cell-based methods for using MSCs in medicine are being actively investigated and tested, especially as carriers for chemotherapeutics, nanoparticles, and photosensitizers. However, despite the inexhaustible regenerative potential and known anticancer properties of MSCs, they may trigger the development and progression of bone tumors. A better understanding of the complex cellular and molecular mechanisms of OS pathogenesis is essential to identify novel molecular effectors involved in oncogenesis. The current review focuses on signaling pathways and miRNAs involved in the development of OS and describes the role of MSCs in oncogenesis and their potential for antitumor cell-based therapy. Full article
(This article belongs to the Special Issue Therapeutic Modulation of Mesenchymal Stem Cell for Effective Regenerative Medicine)
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