Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Adipose-Derived Stem Cell Extra-Cellular Vesicles: Molecular Effects

Print Special Issue Flyer
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 March 2022) | Viewed by 22042

Share This Special Issue

Special Issue Editors

Prof. Dr. Bruce Milthorpe

E-Mail Website
Guest Editor

Faculty of Science, University of Technology Sydney, Sydney, Australia
Interests: bioceramics; biomaterials evaluation techniques; biological molecule adsorption to surfaces; tissue engineering, stem cells
Special Issues, Collections and Topics in MDPI journals

Dr. Jerran Santos

E-Mail Website
Guest Editor

Advanced Tissue Engineering and Stem Cell Biology Group, University of Technology Sydney, Sydney, Australia
Interests: stem cells; regenerative medicine; systems biology; next-generation genome sequencing; bacterial pathogenesis; secreted moonlighting proteins; cytokine and immuno-modulation; 3D molecular modelling; protein interaction network building
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue examines the cell-to-cell communication by extracellular vesicles (ECV) and/or microparticles, from adipose-derived stem cells. ECV and microparticles are secreted by many cell types. They are usually loaded with multiple cargoes that may influence the behavior of surrounding cells that fuse with or endocytose the ECVs. This Special Issue will elucidate both the cargoes and the messages sent by ECVs from ADSCs to either ADSCs or other cells.

All aspects of ECV/microparticle production, cargo choice, secretion mechanisms, uptake, and processing by recipient cells are welcome in this issue. New techniques for identifying and/or quantifying cargoes and variability in cargo depending on size, stimulation, or extracellular matrix properties are also encouraged.

Prof. Dr. Bruce Milthorpe
Dr. Jerran Santos
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

extra-cellular vesicles
cytokines
histones
endocytosis
cell-cell communication

Published Papers (6 papers)

Download All Papers

Research

Jump to: Review

17 pages, 2840 KiB

Open AccessArticle

A Molecular Analysis of Cytokine Content across Extracellular Vesicles, Secretions, and Intracellular Space from Different Site-Specific Adipose-Derived Stem Cells

by Jerran Santos, Penelope V. Dalla and Bruce K. Milthorpe

Int. J. Mol. Sci. 2022, 23(1), 397; https://doi.org/10.3390/ijms23010397 - 30 Dec 2021

Cited by 4 | Viewed by 1891

Abstract

Cytokines are multifunctional small proteins that have a vital influence on inflammatory states of tissues and play a role in signalling and cellular control mechanisms. Cytokine expression has primarily been viewed as a form of direct secretion of molecules through an active transportation; however, other forms of active transport such as extracellular vesicles are at play. This is particularly important in stem cells where signalling molecules are key to communication managing the levels of proliferation, migration, and differentiation into mature cells. This study investigated cytokines from intracellular content, direct cellular secretions, and extracellular vesicles from adult adipose-derived stem cells isolated from three distinct anatomical locations: abdomen, thigh, and chin. The cells were cultured investigated using live cell microscopy, cytokine assays, and bioinformatics analysis. The cytokines quantified and examined from each sample type showed a distinct difference between niche areas and sample types. The varying levels of TNF-alpha, IL-6 and IL-8 cytokines were shown to play a crucial role in signalling pathways such as MAPK, ERK1/2 and JAK-STAT in cells. On the other hand, the chemotactic cytokines IL-1rn, Eotaxin, IP-10 and MCP-1 showed the most prominent changes across extracellular vesicles with roles in noncanonical signalling. By examining the local and tangential roles of cytokines in stem cells, their roles in signalling and in regenerative mechanisms may be further understood. Full article

(This article belongs to the Special Issue Adipose-Derived Stem Cell Extra-Cellular Vesicles: Molecular Effects)

► Show Figures

Figure 1

21 pages, 4701 KiB

Open AccessArticle

Functional Recovery Caused by Human Adipose Tissue Mesenchymal Stem Cell-Derived Extracellular Vesicles Administered 24 h after Stroke in Rats

by Francieli Rohden, Luciele Varaschini Teixeira, Luis Pedro Bernardi, Pamela Cristina Lukasewicz Ferreira, Mariana Colombo, Geciele Rodrigues Teixeira, Fernanda dos Santos de Oliveira, Elizabeth Obino Cirne Lima, Fátima Costa Rodrigues Guma and Diogo Onofre Souza

Int. J. Mol. Sci. 2021, 22(23), 12860; https://doi.org/10.3390/ijms222312860 - 28 Nov 2021

Cited by 8 | Viewed by 2358

Abstract

Ischemic stroke is a major cause of death and disability, intensely demanding innovative and accessible therapeutic strategies. Approaches presenting a prolonged period for therapeutic intervention and new treatment administration routes are promising tools for stroke treatment. Here, we evaluated the potential neuroprotective properties of nasally administered human adipose tissue mesenchymal stem cell (hAT-MSC)-derived extracellular vesicles (EVs) obtained from healthy individuals who underwent liposuction. After a single intranasal EV (200 µg/kg) administered 24 h after a focal permanent ischemic stroke in rats, a higher number of EVs, improvement of the blood–brain barrier, and re-stabilization of vascularization were observed in the recoverable peri-infarct zone, as well as a significant decrease in infarct volume. In addition, EV treatment recovered long-term motor (front paws symmetry) and behavioral impairment (short- and long-term memory and anxiety-like behavior) induced by ischemic stroke. In line with these findings, our work highlights hAT-MSC-derived EVs as a promising therapeutic strategy for stroke. Full article

(This article belongs to the Special Issue Adipose-Derived Stem Cell Extra-Cellular Vesicles: Molecular Effects)

► Show Figures

Figure 1

13 pages, 1895 KiB

Open AccessArticle

Discovery of Lactoferrin as a Stimulant for hADSC-Derived EV Secretion and Proof of Enhancement of Resulting EVs through Skin Model

by Junho Kim, Ga Eun You, Minkyu Woo, Nicole Hyesoo Chang and Jungsun Lee

Int. J. Mol. Sci. 2021, 22(20), 10993; https://doi.org/10.3390/ijms222010993 - 12 Oct 2021

Cited by 5 | Viewed by 1838

Abstract

Extracellular vesicles (EVs) are secreted from hADSCs in low concentrations, which makes it difficult to utilize them for the development of therapeutic products. To overcome the problem associated with low concentration, we proposed human lactoferrin (hLF) as a stimulant for the secretion of hADSC-derived EVs. hLF has been reported to upregulate intracellular Ca²⁺, which is known to be capable of increasing EV secretion. We cultured hADSCs in hLF-supplemented media and analyzed the changes in intracellular Ca²⁺ concentration. The characteristics of hADSC-derived EVs secreted by hLF stimulation were analyzed through their number, membrane protein markers, and the presence of hLFs to EVs. The function of hADSC-derived EVs was investigated through their effects on dermal fibroblasts. We found that hLF helped hADSCs effectively uptake Ca²⁺, resulting in an increase of EVs secretion by more than a factor of 4. The resulting EVs had enhanced proliferation and collagen synthesis effect on dermal fibroblasts when compared to the same number of hADSC-derived EVs secreted without hLF stimulation. The enhanced secretion of hADSC-derived EVs increased collagen synthesis through enhanced epidermal penetration, which resulted from increased EV numbers. In summary, we propose hLF to be a useful stimulant in increasing the secretion rate of hADSC-derived EVs. Full article

(This article belongs to the Special Issue Adipose-Derived Stem Cell Extra-Cellular Vesicles: Molecular Effects)

► Show Figures

Figure 1

26 pages, 7226 KiB

Open AccessArticle

Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes

by Margherita Pomatto, Chiara Gai, Federica Negro, Massimo Cedrino, Cristina Grange, Elena Ceccotti, Gabriele Togliatto, Federica Collino, Marta Tapparo, Federico Figliolini, Tatiana Lopatina, Maria Felice Brizzi and Giovanni Camussi

Int. J. Mol. Sci. 2021, 22(8), 3851; https://doi.org/10.3390/ijms22083851 - 08 Apr 2021

Cited by 105 | Viewed by 6402

Abstract

Extracellular vesicles (EVs) derived from mesenchymal stem cells isolated from both bone marrow (BMSCs) and adipose tissue (ADSCs) show potential therapeutic effects. These vesicles often show a similar beneficial effect on tissue regeneration, but in some contexts, they exert different biological properties. To date, a comparison of their molecular cargo that could explain the different biological effect is not available. Here, we demonstrated that ADSC-EVs, and not BMSC-EVs, promote wound healing on a murine model of diabetic wounds. Besides a general similarity, the bioinformatic analysis of their protein and miRNA cargo highlighted important differences between these two types of EVs. Molecules present exclusively in ADSC-EVs were highly correlated to angiogenesis, whereas those expressed in BMSC-EVs were preferentially involved in cellular proliferation. Finally, in vitro analysis confirmed that both ADSC and BMSC-EVs exploited beneficial effect on cells involved in skin wound healing such as fibroblasts, keratinocytes and endothelial cells, but through different cellular processes. Consistent with the bioinformatic analyses, BMSC-EVs were shown to mainly promote proliferation, whereas ADSC-EVs demonstrated a major effect on angiogenesis. Taken together, these results provide deeper comparative information on the cargo of ADSC-EVs and BMSC-EVs and the impact on regenerative processes essential for diabetic wound healing. Full article

(This article belongs to the Special Issue Adipose-Derived Stem Cell Extra-Cellular Vesicles: Molecular Effects)

► Show Figures

Figure 1

Review

Jump to: Research

14 pages, 309 KiB

Open AccessReview

Therapeutic Potential of Exosomes Derived from Adipose Tissue-Sourced Mesenchymal Stem Cells in the Treatment of Neural and Retinal Diseases

by Carl Randall Harrell, Vladislav Volarevic, Valentin Djonov and Ana Volarevic

Int. J. Mol. Sci. 2022, 23(9), 4487; https://doi.org/10.3390/ijms23094487 - 19 Apr 2022

Cited by 20 | Viewed by 3610

Abstract

Therapeutic agents that are able to prevent or attenuate inflammation and ischemia-induced injury of neural and retinal cells could be used for the treatment of neural and retinal diseases. Exosomes derived from adipose tissue-sourced mesenchymal stem cells (AT-MSC-Exos) are extracellular vesicles that contain neurotrophins, immunoregulatory and angio-modulatory factors secreted by their parental cells. AT-MSC-Exos are enriched with bioactive molecules (microRNAs (miRNAs), enzymes, cytokines, chemokines, immunoregulatory, trophic, and growth factors), that alleviate inflammation and promote the survival of injured cells in neural and retinal tissues. Due to the nano-sized dimension and bilayer lipid envelope, AT-MSC-Exos easily bypass blood–brain and blood–retinal barriers and deliver their cargo directly into the target cells. Accordingly, a large number of experimental studies demonstrated the beneficial effects of AT-MSC-Exos in the treatment of neural and retinal diseases. By delivering neurotrophins, AT-MSC-Exos prevent apoptosis of injured neurons and retinal cells and promote neuritogenesis. AT-MSC-Exos alleviate inflammation in the injured brain, spinal cord, and retinas by delivering immunoregulatory factors in immune cells, suppressing their inflammatory properties. AT-MSC-Exos may act as biological mediators that deliver pro-angiogenic miRNAs in endothelial cells, enabling re-vascularization of ischemic neural and retinal tissues. Herewith, we summarized current knowledge about molecular mechanisms which were responsible for the beneficial effects of AT-MSC-Exos in the treatment of neural and retinal diseases, emphasizing their therapeutic potential in neurology and ophthalmology. Full article

(This article belongs to the Special Issue Adipose-Derived Stem Cell Extra-Cellular Vesicles: Molecular Effects)

25 pages, 1517 KiB

Open AccessReview

Extracellular Vesicles from Adipose Tissue Stem Cells in Diabetes and Associated Cardiovascular Disease; Pathobiological Impact and Therapeutic Potential

by Alina Constantin, Alexandru Filippi, Nicoleta Alexandru, Miruna Nemecz and Adriana Georgescu

Int. J. Mol. Sci. 2020, 21(24), 9598; https://doi.org/10.3390/ijms21249598 - 16 Dec 2020

Cited by 12 | Viewed by 4821

Abstract

Adipose tissue-derived stem cells (ADSCs) are pluripotent mesenchymal stem cells found in relatively high percentages in the adipose tissue and able to self-renew and differentiate into many different types of cells. “Extracellular vesicles (EVs), small membrane vesicular structures released during cell activation, senescence, or apoptosis, act as mediators for long distance communication between cells, transferring their specific bioactive molecules into host target cells”. There is a general consensus on how to define and isolate ADSCs, however, multiple separation and characterization protocols are being used in the present which complicate the results’ integration in a single theory on ADSCs’ and their derived factors’ way of action. Metabolic syndrome and type 2 diabetes mellitus (T2DM) are mainly caused by abnormal adipose tissue size, distribution and metabolism and so ADSCs and their secretory factors such as EVs are currently investigated as therapeutics in these diseases. Moreover, due to their relatively easy isolation and propagation in culture and their differentiation ability, ADSCs are being employed in preclinical studies of implantable devices or prosthetics. This review aims to provide a comprehensive summary of the current knowledge on EVs secreted from ADSCs both as diagnostic biomarkers and therapeutics in diabetes and associated cardiovascular disease, the molecular mechanisms involved, as well as on the use of ADSC differentiation potential in cardiovascular tissue repair and prostheses. Full article

(This article belongs to the Special Issue Adipose-Derived Stem Cell Extra-Cellular Vesicles: Molecular Effects)

► Show Figures