scholarly journals Towards Therapeutic Delivery of Extracellular Vesicles: Strategies forIn VivoTracking and Biodistribution Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Giuliana Di Rocco ◽  
Silvia Baldari ◽  
Gabriele Toietta
Keyword(s):  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Stromal Cells ◽  
Degenerative Diseases ◽  
Systemic Delivery ◽  
Beneficial Effects ◽  
Therapeutic Delivery ◽  
Target Organs ◽  
Target Effects

Extracellular vesicles (EVs), such as microvesicles and exosomes, are membranous structures containing bioactive material released by several cells types, including mesenchymal stem/stromal cells (MSCs). Increasing lines of evidences point to EVs as paracrine mediators of the beneficial effects on tissue remodeling associated with cell therapy. Administration of MSCs-derived EVs has therefore the potential to open new and safer therapeutic avenues, alternative to cell-based approaches, for degenerative diseases. However, an enhanced knowledge aboutin vivoEVs trafficking upon delivery is required before effective clinical translation. Only a few studies have focused on the biodistribution analysis of exogenously administered MSCs-derived EVs. Nevertheless, current strategies forin vivotracking in animal models have provided valuable insights on the biodistribution upon systemic delivery of EVs isolated from several cellular sources, indicating in liver, spleen, and lungs the preferential target organs. Different strategies for targeting EVs to specific tissues to enhance their therapeutic efficacy and reduce possible off-target effects have been investigated. Here, in the context of a possible clinical application of MSC-derived EVs for tissue regeneration, we review the existing strategies forin vivotracking and targeting of EVs isolated from different cellular sources and the studies elucidating the biodistribution of exogenously administered EVs.

In vivo systemic delivery of bone marrow-derived mesenchymal stromal cells results in enhanced fascial wound healing

2006 ◽  
Vol 203 (3) ◽  
pp. S42
Author(s):  
David S. Kwon ◽  
Tina Gao ◽  
Bo Liu ◽  
Deborah Dulchavsky ◽  
Scott Dulchavsky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Systemic Delivery

Effects of the tetrahedral framework nucleic acids on the skeletal muscle regeneration in vitro and in vivo

2020 ◽  
Vol 4 (9) ◽  
pp. 2731-2743
Author(s):  
Yang Gao ◽  
Tianxu Zhang ◽  
Junyao Zhu ◽  
Dexuan Xiao ◽  
Mei Zhang ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Muscle Loss ◽  
Degenerative Diseases ◽  
Tetrahedral Framework ◽  
Volumetric Muscle Loss ◽  
Regeneration In Vitro

The challenges associated with muscle degenerative diseases and volumetric muscle loss (VML) emphasizes the prospects of muscle tissue regeneration.

scholarly journals Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review

2020 ◽  
Vol 21 (3) ◽  
pp. 799 ◽  
Author(s):  
Joanna Lelek ◽  
Ewa K. Zuba-Surma
Keyword(s):  
Adipose Tissue ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Differentiation Potential

Mesenchymal stem/ stromal cells (MSCs) represent progenitor cells of various origin with multiple differentiation potential, representing the most studied population of stem cells in both in vivo pre-clinical and clinical studies. MSCs may be found in many tissue sources including extensively studied adipose tissue (ADSCs) and umbilical cord Wharton’s jelly (UC-MSCs). Most of sanative effects of MSCs are due to their paracrine activity, which includes also release of extracellular vesicles (EVs). EVs are small, round cellular derivatives carrying lipids, proteins, and nucleic acids including various classes of RNAs. Due to several advantages of EVs when compare to their parental cells, MSC-derived EVs are currently drawing attention of several laboratories as potential new tools in tissue repair. This review focuses on pro-regenerative properties of EVs derived from ADSCs and UC-MSCs. We provide a synthetic summary of research conducted in vitro and in vivo by employing animal models and within initial clinical trials focusing on neurological, cardiovascular, liver, kidney, and skin diseases. The summarized studies provide encouraging evidence about MSC-EVs pro-regenerative capacity in various models of diseases, mediated by several mechanisms. Although, direct molecular mechanisms of MSC-EV action are still under investigation, the current growing data strongly indicates their potential future usefulness for tissue repair.

scholarly journals P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment

Blood ◽  
2012 ◽  
Vol 119 (6) ◽  
pp. 1468-1478 ◽  
Author(s):  
Abdel Kareem Azab ◽  
Phong Quang ◽  
Feda Azab ◽  
Costas Pitsillides ◽  
Brian Thompson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Stromal Cells ◽  
Critical Role ◽  
Loss Of Function ◽  
Downstream Signaling ◽  
Target Organs ◽  
Regulation Of Growth

Abstract Interactions between multiple myeloma (MM) cells and the BM microenvironment play a critical role in the pathogenesis of MM and in the development of drug resistance by MM cells. Selectins are involved in extravasation and homing of leukocytes to target organs. In the present study, we focused on adhesion dynamics that involve P-selectin glycoprotein ligand-1 (PSGL-1) on MM cells and its interaction with selectins in the BM microenvironment. We show that PSGL-1 is highly expressed on MM cells and regulates the adhesion and homing of MM cells to cells in the BM microenvironment in vitro and in vivo. This interaction involves both endothelial cells and BM stromal cells. Using loss-of-function studies and the small-molecule pan-selectin inhibitor GMI-1070, we show that PSGL-1 regulates the activation of integrins and downstream signaling. We also document that this interaction regulates MM-cell proliferation in coculture with BM microenvironmental cells and the development of drug resistance. Furthermore, inhibiting this interaction with GMI-1070 enhances the sensitization of MM cells to bortezomib in vitro and in vivo. These data highlight the critical contribution of PSGL-1 to the regulation of growth, dissemination, and drug resistance in MM in the context of the BM microenvironment.

scholarly journals Electrospun PCL/PLA Scaffolds Are More Suitable Carriers of Placental Mesenchymal Stromal Cells Than Collagen/Elastin Scaffolds and Prevent Wound Contraction in a Mouse Model of Wound Healing

2020 ◽  
Vol 8 ◽  
Author(s):  
Eva Vonbrunn ◽  
Marc Mueller ◽  
Melanie Pichlsberger ◽  
Monika Sundl ◽  
Alexander Helmer ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mouse Model ◽  
Stromal Cells ◽  
Wound Care ◽  
Skin Wound ◽  
Beneficial Effects ◽  
New Therapeutic Approaches

Mesenchymal stem/stromal cells (MSCs) exert beneficial effects during wound healing, and cell-seeded scaffolds are a promising method of application. Here, we compared the suitability of a clinically used collagen/elastin scaffold (Matriderm) with an electrospun Poly(ε-caprolactone)/poly(l-lactide) (PCL/PLA) scaffold as carriers for human amnion-derived MSCs (hAMSCs). We created an epidermal-like PCL/PLA scaffold and evaluated its microstructural, mechanical, and functional properties. Sequential spinning of different PCL/PLA concentrations resulted in a wide-meshed layer designed for cell-seeding and a dense-meshed layer for apical protection. The Matriderm and PCL/PLA scaffolds then were seeded with hAMSCs, with or without Matrigel coating. The quantity and quality of the adherent cells were evaluated in vitro. The results showed that hAMSCs adhered to and infiltrated both scaffold types but on day 3, more cells were observed on PCL/PLA than on Matriderm. Apoptosis and proliferation rates were similar for all carriers except the coated Matriderm, where apoptotic cells were significantly enhanced. On day 8, the number of cells decreased on all carrier types except the coated Matriderm, which had consistently low cell numbers. Uncoated Matriderm had the highest percentage of proliferative cells and lowest apoptosis rate of all carrier types. Each carrier also was topically applied to skin wound sites in a mouse model and analyzed in vivo over 14 days via optical imaging and histological methods, which showed detectable hAMSCs on all carrier types on day 8. On day 14, all wounds exhibited newly formed epidermis, and all carriers were well-integrated into the underlying dermis and showing signs of degradation. However, only wounds treated with uncoated PCL/PLA maintained a round appearance with minimal contraction. Overall, the results support a 3-day in vitro culture of scaffolds with hAMSCs before wound application. The PCL/PLA scaffold showed higher cell adherence than Matriderm, and the effect of the Matrigel coating was negligible, as all carrier types maintained sufficient numbers of transplanted cells in the wound area. The anti-contractive effects of the PCL/PLA scaffold offer potential new therapeutic approaches to wound care.

scholarly journals Chondrogenic Potential of Dental-Derived Mesenchymal Stromal Cells

Osteology ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 149-174
Author(s):  
Naveen Jeyaraman ◽  
Gollahalli Shivashankar Prajwal ◽  
Madhan Jeyaraman ◽  
Sathish Muthu ◽  
Manish Khanna
Keyword(s):  
Tissue Engineering ◽  
Mesenchymal Stromal Cells ◽  
Tissue Regeneration ◽  
Stromal Cells ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Dentin Matrix

The field of tissue engineering has revolutionized the world in organ and tissue regeneration. With the robust research among regenerative medicine experts and researchers, the plausibility of regenerating cartilage has come into the limelight. For cartilage tissue engineering, orthopedic surgeons and orthobiologists use the mesenchymal stromal cells (MSCs) of various origins along with the cytokines, growth factors, and scaffolds. The least utilized MSCs are of dental origin, which are the richest sources of stromal and progenitor cells. There is a paradigm shift towards the utilization of dental source MSCs in chondrogenesis and cartilage regeneration. Dental-derived MSCs possess similar phenotypes and genotypes like other sources of MSCs along with specific markers such as dentin matrix acidic phosphoprotein (DMP) -1, dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP), and STRO-1. Concerning chondrogenicity, there is literature with marginal use of dental-derived MSCs. Various studies provide evidence for in-vitro and in-vivo chondrogenesis by dental-derived MSCs. With such evidence, clinical trials must be taken up to support or refute the evidence for regenerating cartilage tissues by dental-derived MSCs. This article highlights the significance of dental-derived MSCs for cartilage tissue regeneration.

scholarly journals miR-4732-3p in Extracellular Vesicles From Mesenchymal Stromal Cells Is Cardioprotective During Myocardial Ischemia

2021 ◽  
Vol 9 ◽  
Author(s):  
Rafael Sánchez-Sánchez ◽  
Marta Gómez-Ferrer ◽  
Ignacio Reinal ◽  
Marc Buigues ◽  
Estela Villanueva-Bádenas ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Transforming Growth Factor Beta ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Lentiviral Vector ◽  
Glucose Deprivation ◽  
Scar Tissue

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are an emerging alternative to cell-based therapies to treat many diseases. However, the complexity of producing homogeneous populations of EVs in sufficient amount hampers their clinical use. To address these limitations, we immortalized dental pulp-derived MSC using a human telomerase lentiviral vector and investigated the cardioprotective potential of a hypoxia-regulated EV-derived cargo microRNA, miR-4732-3p. We tested the compared the capacity of a synthetic miR-4732-3p mimic with EVs to confer protection to cardiomyocytes, fibroblasts and endothelial cells against oxygen-glucose deprivation (OGD). Results showed that OGD-induced cardiomyocytes treated with either EVs or miR-4732-3p showed prolonged spontaneous beating, lowered ROS levels, and less apoptosis. Transfection of the miR-4732-3p mimic was more effective than EVs in stimulating angiogenesis in vitro and in vivo and in reducing fibroblast differentiation upon transforming growth factor beta treatment. Finally, the miR-4732-3p mimic reduced scar tissue and preserved cardiac function when transplanted intramyocardially in infarcted nude rats. Overall, these results indicate that miR-4732-3p is regulated by hypoxia and exerts cardioprotective actions against ischemic insult, with potential application in cell-free-based therapeutic strategies.

scholarly journals Potential target for mitigation of COVID-19 by food-derived bioactive peptides

2021 ◽  
Vol 16 ◽  
Author(s):  
Kenji Sato
Keyword(s):  
Bioactive Peptides ◽  
Protein Hydrolysate ◽  
Renin Angiotensin System ◽  
The Body ◽  
Food Protein ◽  
Beneficial Effects ◽  
Target Organs ◽  
Acid Metabolites ◽  
Therapeutic Activities

Oral administration of food protein hydrolysate and naturally occurring peptides exert beneficial effects beyond conventional nutritional functions by supplying amino acids for protein synthesis. These peptides are referred to as food-derived bioactive peptides. The coronavirus disease 2019 (COVID-19) is caused by sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some host and viral proteins are involved in the entry of SARS-CoV-2 into cells and their replication. Peptides with specific sequences can interact with these proteins and have potential prophylactic and therapeutic activities against COVID-19. However, it is difficult to deliver food-derived peptides to target organs without degradation by exopeptidases in the body. Alternatively, food-derived peptides and amino acid metabolites have been suggested to decrease risk factors of COVID-19 by modulating the renin-angiotensin system, the innate immune system, and the antioxidant system. This mini-review is based on in vivo responses to food-derived peptides and aims to introduce potential targets for these peptides in decreasing the risk and severity of COVID-19. 

scholarly journals Plant-Derived Extracellular Vesicles as Therapeutic Nanocarriers

2021 ◽  
Vol 23 (1) ◽  
pp. 191
Author(s):  
Theodora Karamanidou ◽  
Alexander Tsouknidas
Keyword(s):  
Extracellular Vesicles ◽  
Functional Materials ◽  
Physicochemical Characteristics ◽  
Eukaryotic Cell ◽  
Therapeutic Modalities ◽  
Therapeutic Delivery ◽  
Nutraceutical Compounds ◽  
Novel Applications

Mammalian exosomes have emerged as a promising class of functional materials, inspiring novel applications as therapeutic vehicles and nutraceutical compounds. Despite this, their immunogenicity has been an issue of controversy within the scientific community. Although, exosome-like vesicles, innately formed in plants and inherent to eukaryotic cell-derived vesicles, could soothe most of the concerns, they are notably underutilized as therapeutic modalities. This review highlights all efforts published so far, on the use of plant-derived extracellular vesicles (EVs) as therapeutic delivery systems. A summary of the physicochemical characteristics of plant-derived EVs is provided along with their main biological composition and in vitro/in vivo evidence of their therapeutic efficacy provided where available. Despite only a hand full of clinical trials being underway, concerning these vesicles, they arguably possess significant potential as nanodelivery systems of natural origin.

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