scholarly journals Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 991 ◽  
Author(s):  
Dimitrios Tsiapalis ◽  
Lorraine O’Driscoll

Mesenchymal stem cells (MSCs) are being extensively investigated for their potential in tissue engineering and regenerative medicine. However, recent evidence suggests that the beneficial effects of MSCs may be manifest by their released extracellular vesicles (EVs); typically not requiring the administration of MSCs. This evidence, predominantly from pre-clinical in vitro and in vivo studies, suggests that MSC-EVs may exhibit substantial therapeutic properties in many pathophysiological conditions, potentially restoring an extensive range of damaged or diseased tissues and organs. These benefits of MSC EVs are apparently found, regardless of the anatomical or body fluid origin of the MSCs (and include e.g., bone marrow, adipose tissue, umbilical cord, urine, etc). Furthermore, early indications suggest that the favourable effects of MSC-EVs could be further enhanced by modifying the way in which the donor MSCs are cultured (for example, in hypoxic compared to normoxic conditions, in 3D compared to 2D culture formats) and/or if the EVs are subsequently bio-engineered (for example, loaded with specific cargo). So far, few human clinical trials of MSC-EVs have been conducted and questions remain unanswered on whether the heterogeneous population of EVs is beneficial or some specific sub-populations, how best we can culture and scale-up MSC-EV production and isolation for clinical utility, and in what format they should be administered. However, as reviewed here, there is now substantial evidence supporting the use of MSC-EVs in tissue engineering and regenerative medicine and further research to establish how best to exploit this approach for societal and economic benefit is warranted.

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ashley G. Zhao ◽  
Kiran Shah ◽  
Brett Cromer ◽  
Huseyin Sumer

Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles, which act as shuttles, delivering a range of biomolecules to diverse target cells. They play an important role in maintenance of biophysiological homeostasis and cellular, physiological, and pathological processes. EVs have significant diagnostic and therapeutic potentials and have been studied both in vitro and in vivo in many fields. Mesenchymal stem cells (MSCs) are multipotent cells with many therapeutic applications and have also gained much attention as prolific producers of EVs. MSC-derived EVs are being explored as a therapeutic alternative to MSCs since they may have similar therapeutic effects but are cell-free. They have applications in regenerative medicine and tissue engineering and, most importantly, confer several advantages over cells such as lower immunogenicity, capacity to cross biological barriers, and less safety concerns. In this review, we introduce the biogenesis of EVs, including exosomes and microvesicles. We then turn more specifically to investigations of MSC-derived EVs. We highlight the great therapeutic potential of MSC-derived EVs and applications in regenerative medicine and tissue engineering.


Polymers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 2529
Author(s):  
Mojtaba Shafiei ◽  
Mohamed Nainar Mohamed Ansari ◽  
Saiful Izwan Abd Razak ◽  
Muhammad Umar Aslam Khan

Tissue engineering and regenerative medicine are generally concerned with reconstructing cells, tissues, or organs to restore typical biological characteristics. Liposomes are round vesicles with a hydrophilic center and bilayers of amphiphiles which are the most influential family of nanomedicine. Liposomes have extensive research, engineering, and medicine uses, particularly in a drug delivery system, genes, and vaccines for treatments. Exosomes are extracellular vesicles (EVs) that carry various biomolecular cargos such as miRNA, mRNA, DNA, and proteins. As exosomal cargo changes with adjustments in parent cells and position, research of exosomal cargo constituents provides a rare chance for sicknesses prognosis and care. Exosomes have a more substantial degree of bioactivity and immunogenicity than liposomes as they are distinctly chiefly formed by cells, which improves their steadiness in the bloodstream, and enhances their absorption potential and medicinal effectiveness in vitro and in vivo. In this review, the crucial challenges of exosome and liposome science and their functions in disease improvement and therapeutic applications in tissue engineering and regenerative medicine strategies are prominently highlighted.


2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.


2021 ◽  
Vol 14 (4) ◽  
pp. 336
Author(s):  
Annalisa Noce ◽  
Maria Albanese ◽  
Giulia Marrone ◽  
Manuela Di Lauro ◽  
Anna Pietroboni Zaitseva ◽  
...  

The Coronavirus Disease-19 (COVID-19) pandemic has caused more than 100,000,000 cases of coronavirus infection in the world in just a year, of which there were 2 million deaths. Its clinical picture is characterized by pulmonary involvement that culminates, in the most severe cases, in acute respiratory distress syndrome (ARDS). However, COVID-19 affects other organs and systems, including cardiovascular, urinary, gastrointestinal, and nervous systems. Currently, unique-drug therapy is not supported by international guidelines. In this context, it is important to resort to adjuvant therapies in combination with traditional pharmacological treatments. Among natural bioactive compounds, palmitoylethanolamide (PEA) seems to have potentially beneficial effects. In fact, the Food and Drug Administration (FDA) authorized an ongoing clinical trial with ultramicronized (um)-PEA as an add-on therapy in the treatment of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. In support of this hypothesis, in vitro and in vivo studies have highlighted the immunomodulatory, anti-inflammatory, neuroprotective and pain-relieving effects of PEA, especially in its um form. The purpose of this review is to highlight the potential use of um-PEA as an adjuvant treatment in SARS-CoV-2 infection.


2021 ◽  
Vol 11 (5) ◽  
pp. 336
Author(s):  
Mohammed Ghiboub ◽  
Ahmed M. I. Elfiky ◽  
Menno P. J. de Winther ◽  
Nicola R. Harker ◽  
David F. Tough ◽  
...  

Histone deacetylases (HDACs) and bromodomain-containing proteins (BCPs) play a key role in chromatin remodeling. Based on their ability to regulate inducible gene expression in the context of inflammation and cancer, HDACs and BCPs have been the focus of drug discovery efforts, and numerous small-molecule inhibitors have been developed. However, dose-limiting toxicities of the first generation of inhibitors, which typically target multiple HDACs or BCPs, have limited translation to the clinic. Over the last decade, an increasing effort has been dedicated to designing class-, isoform-, or domain-specific HDAC or BCP inhibitors, as well as developing strategies for cell-specific targeted drug delivery. Selective inhibition of the epigenetic modulators is helping to elucidate the functions of individual epigenetic proteins and has the potential to yield better and safer therapeutic strategies. In accordance with this idea, several in vitro and in vivo studies have reported the ability of more selective HDAC/BCP inhibitors to recapitulate the beneficial effects of pan-inhibitors with less unwanted adverse events. In this review, we summarize the most recent advances with these strategies, discussing advantages and limitations of these approaches as well as some therapeutic perspectives, focusing on autoimmune and inflammatory diseases.


Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Raghubendra Singh Dagur ◽  
Moses New-Aaron ◽  
Murali Ganesan ◽  
Weimin Wang ◽  
Svetlana Romanova ◽  
...  

Background: Alcohol abuse is common in people living with HIV-1 and dramaticallyenhances the severity of HIV-induced liver damage by inducing oxidative stress and lysosomaldysfunction in the liver cells. We hypothesize that the increased release of extracellular vesicles(EVs) in hepatocytes and liver humanized mouse model is linked to lysosome dysfunction. Methods:The study was performed on primary human hepatocytes and human hepatoma RLWXP-GFP (Huh7.5 cells stably transfected with CYP2E1 and XPack-GFP) cells and validated on ethanol-fed liverhumanizedfumarylacetoacetate hydrolase (Fah)-/-, Rag2-/-, common cytokine receptor gamma chainknockout (FRG-KO) mice. Cells and mice were infected with HIV-1ADA virus. Results: We observedan increase in the secretion of EVs associated with a decrease in lysosomal activity and expressionof lysosomal-associated membrane protein 1. Next-generation RNA sequencing of primary humanhepatocytes revealed 63 differentially expressed genes, with 13 downregulated and 50 upregulatedgenes in the alcohol–HIV-treated group. Upstream regulator analysis of differentially expressedgenes through Ingenuity Pathway Analysis identified transcriptional regulators affecting downstreamgenes associated with increased oxidative stress, lysosomal associated disease, and function andEVs biogenesis. Our in vitro findings were corroborated by in vivo studies on human hepatocytetransplantedhumanized mice, indicating that intensive EVs’ generation by human hepatocytes andtheir secretion to serum was associated with increased oxidative stress and reduction in lysosomalactivities triggered by HIV infection and ethanol diet. Conclusion: HIV-and-ethanol-metabolisminducedEVs release is tightly controlled by lysosome status in hepatocytes and participates in thedevelopment of double-insult-induced liver injury.


2009 ◽  
Vol 21 (03) ◽  
pp. 149-155 ◽  
Author(s):  
Hsu-Wei Fang

Cartilage injuries may be caused by trauma, biomechanical imbalance, or degenerative changes of joint. Unfortunately, cartilage has limited capability to spontaneous repair once damaged and may lead to progressive damage and degeneration. Cartilage tissue-engineering techniques have emerged as the potential clinical strategies. An ideal tissue-engineering approach to cartilage repair should offer good integration into both the host cartilage and the subchondral bone. Cells, scaffolds, and growth factors make up the tissue engineering triad. One of the major challenges for cartilage tissue engineering is cell source and cell numbers. Due to the limitations of proliferation for mature chondrocytes, current studies have alternated to use stem cells as a potential source. In the recent years, a lot of novel biomaterials has been continuously developed and investigated in various in vitro and in vivo studies for cartilage tissue engineering. Moreover, stimulatory factors such as bioactive molecules have been explored to induce or enhance cartilage formation. Growth factors and other additives could be added into culture media in vitro, transferred into cells, or incorporated into scaffolds for in vivo delivery to promote cellular differentiation and tissue regeneration.Based on the current development of cartilage tissue engineering, there exist challenges to overcome. How to manipulate the interactions between cells, scaffold, and signals to achieve the moderation of implanted composite differentiate into moderate stem cells to differentiate into hyaline cartilage to perform the optimum physiological and biomechanical functions without negative side effects remains the target to pursue.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hyuck Joon Kwon

The prevalent nature of osteoarthritis that causes the erosion of joint surfaces and loss of mobility and muscle dystrophy that weakens the musculoskeletal system and hampers locomotion underlies the importance of developing functional replacement or regeneration of muscle and cartilage tissues. Polyelectrolyte gels have high potential as cellular scaffolds due to characteristic properties similar to biological matrixes. A number of in vitro and in vivo studies demonstrated that polyelectrolyte gels are useful for replacement and regeneration of muscle and cartilage tissues. In addition, it was also found that polyelectrolyte gels have high biocompatibility, durability, and resistance to biodegradation. Moreover, polyelectrolyte gels can overcome their drawbacks of mechanical behavior by introducing double network into the gel. This paper reviews the current status and recent progress of polyelectrolyte gel-based tissue engineering for repairs of muscle and cartilage tissues.


2020 ◽  
Vol 9 ◽  
pp. 1743
Author(s):  
Solmaz Rahmani Barouji ◽  
Amir Saber ◽  
Mohammadali Torbati ◽  
Seyyed Mohammad Bagher Fazljou ◽  
Ahmad Yari Khosroushahi

raditional medicine (TM) that developed over the years within various societies consists of medical experimental knowledge and practices, which apply natural methods and compounds for general wellness and healing. Moomiaii as a pale-brown to blackish-brown natural exudate is one of the natural compounds in traditional medicine that has been used over 3000 years in many countries of the world especially in India, China, Russia, Iran, Mongolia, Kazakhstan and Kirgizstan. We reviewed all English-language studies about Moomiaii that we accessed them. In traditional medicine, many beneficial activities have been attributed to Moomiaii and to its main constituents, Humic acid and Fulvic acid, which are widely used to prevent and treatment of different diseases. Some modern scientific investigations showed that Moomiaii as a safe dietary supplement can be beneficial in various health complications. Even though the beneficial effects of Moomiaii have been confirmed in traditional and modern medicine, it seems that additional in-vitro/in-vivo studies and comprehensive clinical trials are necessary to explain the whole mechanisms of action and to determine the effective doses in various diseases. We discuss and clarify the claimed health beneficial effects of Moomiaii in some wide-spread diseases regarding its anti-ulcerogenic, immunomodulatory, antidiabetic, antioxidative and anticancer properties. [GMJ.2020;9:e1743]


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