Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair

Special Issue Editors
Special Issue Information
Keywords
Published Papers

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: closed (31 August 2022) | Viewed by 17567

Share This Special Issue

Special Issue Editor

Dr. Joan Oliva

E-Mail Website
Guest Editor

Department of Clinical Research, Emmaus Medical, Inc., Torrance, CA 90503, USA
Interests: stem cells; tissue regeneration; cell therapy; vitrification
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleague,

Stem cell therapy has been developed in the past decades for the treatment of genetic and non-genetic diseases. Stem cells are usually injected or transplanted after assembling single cells in an organoid (spheres, cell sheets, etc.), with therapeutic variable success. It was believed that stem cells were directly involved in the treatment of diseases or organs, but recently, increasing evidence suggests that stem cells may act via a paracrine effect, through the production and release of extracellular vesicles (EV). EV are nanovesicles containing proteins, nucleic acids (miRNA, RNA), lipids that will modify the activities of their target cells. These important signal mediators could be used to promote the recovery of damaged organs, decrease ischemia–reperfusion injuries, manage and control immunoreactions (acute or chronic), target drugs. The use of EV in treating patients is so important that clinical trials are already being conducted in various hospitals.

This Special Issue will host reviews and articles from scientists who have been studying extracellular vesicles. Topics of interest include, but are not limited to, all potential medical applications of extracellular vesicles and processes related to vesicles, such as their transport, production, etc.

Dr. Joan Oliva
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

Extracellular Vesicles
Stem Cells
Therapies
Paracrine
Inflammation
Ischemia
Organ Healing

Published Papers (6 papers)

Download All Papers

Editorial

Jump to: Research

4 pages, 328 KiB

Open AccessEditorial

Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair

by Joan Oliva

Int. J. Mol. Sci. 2023, 24(5), 4798; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054798 - 02 Mar 2023

Viewed by 1098

Abstract

The purpose of this Special Issue is to emphasize the great potential of the translational applications of extracellular vesicles (EVs) produced by stem cells (mesenchymal stem cells, induced pluripotent stem cells, etc [...] Full article

(This article belongs to the Special Issue Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair)

► Show Figures

Figure 1

Research

Jump to: Editorial

25 pages, 3248 KiB

Open AccessArticle

Scalable Generation of Nanovesicles from Human-Induced Pluripotent Stem Cells for Cardiac Repair

by Jonathan Lozano, Alin Rai, Jarmon G. Lees, Haoyun Fang, Bethany Claridge, Shiang Y. Lim and David W. Greening

Int. J. Mol. Sci. 2022, 23(22), 14334; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232214334 - 18 Nov 2022

Cited by 16 | Viewed by 3553

Abstract

Extracellular vesicles (EVs) from stem cells have shown significant therapeutic potential to repair injured cardiac tissues and regulate pathological fibrosis. However, scalable generation of stem cells and derived EVs for clinical utility remains a huge technical challenge. Here, we report a rapid size-based extrusion strategy to generate EV-like membranous nanovesicles (NVs) from easily sourced human iPSCs in large quantities (yield 900× natural EVs). NVs isolated using density-gradient separation (buoyant density 1.13 g/mL) are spherical in shape and morphologically intact and readily internalised by human cardiomyocytes, primary cardiac fibroblasts, and endothelial cells. NVs captured the dynamic proteome of parental cells and include pluripotency markers (LIN28A, OCT4) and regulators of cardiac repair processes, including tissue repair (GJA1, HSP20/27/70, HMGB1), wound healing (FLNA, MYH9, ACTC1, ILK), stress response/translation initiation (eIF2S1/S2/S3/B4), hypoxia response (HMOX2, HSP90, GNB1), and extracellular matrix organization (ITGA6, MFGE8, ITGB1). Functionally, NVs significantly promoted tubule formation of endothelial cells (angiogenesis) (p < 0.05) and survival of cardiomyocytes exposed to low oxygen conditions (hypoxia) (p < 0.0001), as well as attenuated TGF-β mediated activation of cardiac fibroblasts (p < 0.0001). Quantitative proteome profiling of target cell proteome following NV treatments revealed upregulation of angiogenic proteins (MFGE8, MYH10, VDAC2) in endothelial cells and pro-survival proteins (CNN2, THBS1, IGF2R) in cardiomyocytes. In contrast, NVs attenuated TGF-β-driven extracellular matrix remodelling capacity in cardiac fibroblasts (ACTN1, COL1A1/2/4A2/12A1, ITGA1/11, THBS1). This study presents a scalable approach to generating functional NVs for cardiac repair. Full article

(This article belongs to the Special Issue Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair)

► Show Figures

Graphical abstract

17 pages, 2948 KiB

Open AccessArticle

Mesenchymal Stem Cell-Derived Extracellular Vesicles as Proposed Therapy in a Rat Model of Cerebral Small Vessel Disease

by Reut Guy, Shay Herman, Hadar Benyamini, Tali Ben-Zur, Hila Kobo, Metsada Pasmanik-Chor, Dafna Yaacobi, Eric Barel, Chana Yagil, Yoram Yagil and Daniel Offen

Int. J. Mol. Sci. 2022, 23(19), 11211; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911211 - 23 Sep 2022

Cited by 5 | Viewed by 1909

Abstract

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been employed in the past decade as therapeutic agents in various diseases, including central nervous system (CNS) disorders. We currently aimed to use MSC-EVs as potential treatment for cerebral small vessel disease (CSVD), a complex disorder with a variety of manifestations. MSC-EVs were intranasally administrated to salt-sensitive hypertension prone SBH/y rats that were DOCA-salt loaded (SBH/y-DS), which we have previously shown is a model of CSVD. MSC-EVs accumulated within brain lesion sites of SBH/y-DS. An in vitro model of an inflammatory environment in the brain demonstrated anti-inflammatory properties of MSC-EVs. Following in vivo MSC-EV treatment, gene set enrichment analysis (GSEA) of SBH/y-DS cortices revealed downregulation of immune system response-related gene sets. In addition, MSC-EVs downregulated gene sets related to apoptosis, wound healing and coagulation, and upregulated gene sets associated with synaptic signaling and cognition. While no specific gene was markedly altered upon treatment, the synergistic effect of all gene alternations was sufficient to increase animal survival and improve the neurological state of affected SBH/y-DS rats. Our data suggest MSC-EVs act as microenvironment modulators, through various molecular pathways. We conclude that MSC-EVs may serve as beneficial therapeutic measure for multifactorial disorders, such as CSVD. Full article

(This article belongs to the Special Issue Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair)

► Show Figures

Figure 1

21 pages, 3893 KiB

Open AccessArticle

CD73-Adenosinergic Axis Mediates the Protective Effect of Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Ischemic Renal Damage in a Rat Model of Donation after Circulatory Death

by Maria Antonietta Grignano, Stefania Bruno, Simona Viglio, Maria Antonietta Avanzini, Marta Tapparo, Marina Ramus, Stefania Croce, Chiara Valsecchi, Eleonora Francesca Pattonieri, Gabriele Ceccarelli, Federica Manzoni, Annalia Asti, Carmelo Libetta, Vincenzo Sepe, Paolo Iadarola, Marilena Gregorini and Teresa Rampino

Int. J. Mol. Sci. 2022, 23(18), 10681; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810681 - 14 Sep 2022

Cited by 5 | Viewed by 1686

Abstract

We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system. Full article

(This article belongs to the Special Issue Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair)

► Show Figures

Graphical abstract

24 pages, 7862 KiB

Open AccessArticle

Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice

by Stella Chin-Shaw Tsai, Kuender D. Yang, Kuang-Hsi Chang, Frank Cheau-Feng Lin, Ruey-Hwang Chou, Min-Chih Li, Ching-Chang Cheng, Chien-Yu Kao, Chie-Pein Chen, Hung-Ching Lin and Yi-Chao Hsu

Int. J. Mol. Sci. 2021, 22(13), 6664; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136664 - 22 Jun 2021

Cited by 26 | Viewed by 4454

Abstract

Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 μg/μL) injection at the same time point; and (ii) UCMSC exosome (1.2 μg/μL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair. Full article

(This article belongs to the Special Issue Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair)

► Show Figures

Figure 1

16 pages, 21265 KiB

Open AccessArticle

Mesenchymal Stem Cell-Derived Extracellular Vesicles Protect Human Corneal Endothelial Cells from Endoplasmic Reticulum Stress-Mediated Apoptosis

by Lola Buono, Simona Scalabrin, Marco De Iuliis, Adele Tanzi, Cristina Grange, Marta Tapparo, Raffaele Nuzzi and Benedetta Bussolati

Int. J. Mol. Sci. 2021, 22(9), 4930; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094930 - 06 May 2021

Cited by 24 | Viewed by 3809

Abstract

Corneal endothelial dystrophy is a relevant cause of vision loss and corneal transplantation worldwide. In the present study, we analyzed the effect of mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) in an in vitro model of corneal dystrophy, characterized by endoplasmic reticulum stress. The effects of MSC-EVs were compared with those of serum-derived EVs, reported to display a pro-angiogenic activity. MSC-EVs were able to induce a significant down-regulation of the large majority of endoplasmic reticulum stress-related genes in human corneal endothelial cells after exposure to serum deprivation and tunicamycin. In parallel, they upregulated the Akt pathway and limited caspase-3 activation and apoptosis. At variance, the effect of the serum EVs was mainly limited to Akt phosphorylation, with minimal or absent effects on endoplasmic reticulum stress modulation and apoptosis prevention. The effects of MSC-EVs were correlated to the transfer of numerous endoplasmic reticulum (ER)-stress targeting miRNAs to corneal endothelial cells. These data suggest a potential therapeutic effect of MSC-EVs for corneal endothelial endoplasmic reticulum stress, a major player in corneal endothelial dystrophy. Full article

(This article belongs to the Special Issue Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair)

► Show Figures