scholarly journals Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures

2019 ◽  
Vol 116 (5) ◽  
pp. 1569-1578 ◽  
Author(s):  
Minwook Kim ◽  
David R. Steinberg ◽  
Jason A. Burdick ◽  
Robert L. Mauck
Keyword(s):  
Functional Outcomes ◽  
Cell Types ◽  
Functional Differentiation ◽  
Extracellular Vesicle ◽  
Transport Mechanisms ◽  
Close Proximity ◽  
Effective Delivery ◽  
Matrix Production ◽  
Engineered Cartilage ◽  
Adult Mscs

Several recent studies have demonstrated that coculture of chondrocytes (CHs) with bone marrow-derived mesenchymal stem cells (MSCs) improves their chondrogenesis. This implies that intercellular communication dictates fate decisions in recipient cells and/or reprograms their metabolic state to support a differentiated function. While this coculture phenomenon is compelling, the differential chondroinductivity of zonal CHs on MSC cocultures, the nature of the molecular cargo, and their transport mechanisms remains undetermined. Here, we demonstrate that juvenile CHs in coculture with adult MSCs promote functional differentiation and improved matrix production. We further demonstrate that close proximity between the two cell types is a prerequisite for this response and that the outcome of this interaction improves viability, chondrogenesis, matrix formation, and homeostasis in the recipient MSCs. Furthermore, we visualized the transfer of intracellular contents from CHs to nearby MSCs and showed that inhibition of extracellular vesicle (EV) transfer blocks the synergistic effect of coculture, identifying EVs as the primary mode of communication in these cocultures. These findings will forward the development of therapeutic agents and more effective delivery systems to promote cartilage repair.

scholarly journals Extracellular-Vesicle-Based Coatings Enhance Bioactivity of Titanium Implants—SurfEV

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1445
Author(s):  
Taisa Nogueira Pansani ◽  
Thanh Huyen Phan ◽  
Qingyu Lei ◽  
Alexey Kondyurin ◽  
Bill Kalionis ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Titanium Surface ◽  
Wound Closure ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Tissue Growth ◽  
Titanium Implants ◽  
The Body ◽  
High Concentrations ◽  
And Migration

Extracellular vesicles (EVs) are nanoparticles released by cells that contain a multitude of biomolecules, which act synergistically to signal multiple cell types. EVs are ideal candidates for promoting tissue growth and regeneration. The tissue regenerative potential of EVs raises the tantalizing possibility that immobilizing EVs on implant surfaces could potentially generate highly bioactive and cell-instructive surfaces that would enhance implant integration into the body. Such surfaces could address a critical limitation of current implants, which do not promote bone tissue formation or bond bone. Here, we developed bioactive titanium surface coatings (SurfEV) using two types of EVs: secreted by decidual mesenchymal stem cells (DEVs) and isolated from fermented papaya fluid (PEVs). For each EV type, we determined the size, morphology, and molecular composition. High concentrations of DEVs enhanced cell proliferation, wound closure, and migration distance of osteoblasts. In contrast, the cell proliferation and wound closure decreased with increasing concentration of PEVs. DEVs enhanced Ca/P deposition on the titanium surface, which suggests improvement in bone bonding ability of the implant (i.e., osteointegration). EVs also increased production of Ca and P by osteoblasts and promoted the deposition of mineral phase, which suggests EVs play key roles in cell mineralization. We also found that DEVs stimulated the secretion of secondary EVs observed by the presence of protruding structures on the cell membrane. We concluded that, by functionalizing implant surfaces with specialized EVs, we will be able to enhance implant osteointegration by improving hydroxyapatite formation directly at the surface and potentially circumvent aseptic loosening of implants.

scholarly journals First blood: the endothelial origins of hematopoietic progenitors

Angiogenesis ◽  
2021 ◽  
Author(s):  
Giovanni Canu ◽  
Christiana Ruhrberg
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Fetal Liver ◽  
Cell Types ◽  
Yolk Sac ◽  
Vascular Endothelial ◽  
Hematopoietic Stem ◽  
Close Proximity ◽  
Clinical Interest

AbstractHematopoiesis in vertebrate embryos occurs in temporally and spatially overlapping waves in close proximity to blood vascular endothelial cells. Initially, yolk sac hematopoiesis produces primitive erythrocytes, megakaryocytes, and macrophages. Thereafter, sequential waves of definitive hematopoiesis arise from yolk sac and intraembryonic hemogenic endothelia through an endothelial-to-hematopoietic transition (EHT). During EHT, the endothelial and hematopoietic transcriptional programs are tightly co-regulated to orchestrate a shift in cell identity. In the yolk sac, EHT generates erythro-myeloid progenitors, which upon migration to the liver differentiate into fetal blood cells, including erythrocytes and tissue-resident macrophages. In the dorsal aorta, EHT produces hematopoietic stem cells, which engraft the fetal liver and then the bone marrow to sustain adult hematopoiesis. Recent studies have defined the relationship between the developing vascular and hematopoietic systems in animal models, including molecular mechanisms that drive the hemato-endothelial transcription program for EHT. Moreover, human pluripotent stem cells have enabled modeling of fetal human hematopoiesis and have begun to generate cell types of clinical interest for regenerative medicine.

Tissue-Engineered Cartilage in Three-Dimensional Cultured Chondrocytes by Ultrasound Stimulation and Collagen Sponge as Scaffold

2009 ◽  
Author(s):  
Toshihiko Shiraishi ◽  
Ietomo Matsunaga ◽  
Shin Morishita ◽  
Ryohei Takeuchi ◽  
Tomoyuki Saito ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Three Dimensional ◽  
Collagen Sponge ◽  
Cartilage Tissue ◽  
Mechanical Environment ◽  
Ultrasound Stimulation ◽  
Scaffold Structure ◽  
Matrix Production ◽  
Engineered Cartilage ◽  
Cultured Chondrocytes

This paper describes the effects of ultrasound stimulation on chondrocytes in three-dimensional culture in relation to the production of regenerative cartilage tissue, using collagen sponges as a carrier and supplementation with hyaluronic acid (used in the conservative treatment of osteoarthritis). It has been shown that cell proliferation and matrix production can be facilitated by considering the mechanical environment of the cultured chondrocytes and the mechanical properties of the scaffold structure used in the culture and of the stimulation used.

Subcellular localization of the Na+/H+ exchanger NHE1 in rat myocardium

1999 ◽  
Vol 276 (2) ◽  
pp. H709-H717 ◽  
Author(s):  
Kevin Petrecca ◽  
Roxana Atanasiu ◽  
Sergio Grinstein ◽  
John Orlowski ◽  
Alvin Shrier
Keyword(s):  
Connexin 43 ◽  
Cell Types ◽  
Ph Homeostasis ◽  
Adult Rat ◽  
Junction Protein ◽  
Close Proximity ◽  
Gap Junction Protein ◽  
Intercalated Disks ◽  
Distinct Distribution ◽  
Intercalated Disk

The Na+/H+exchanger NHE1 isoform is an integral component of cardiac intracellular pH homeostasis that is critically important for myocardial contractility. To gain further insight into its physiological significance, we determined its cellular distribution in adult rat heart by using immunohistochemistry and confocal microscopy. NHE1 was localized predominantly at the intercalated disk regions in close proximity to the gap junction protein connexin 43 of atrial and ventricular muscle cells. Significant labeling of NHE1 was also observed along the transverse tubular systems, but not the lateral sarcolemmal membranes, of both cell types. In contrast, the Na+-K+-ATPase α1-subunit was readily labeled by a specific mouse monoclonal antibody (McK1) along the entire ventricular sarcolemma and intercalated disks and, to a lesser extent, in the transverse tubules. These results indicate that NHE1 has a distinct distribution in heart and may fulfill specialized roles by selectively regulating the pH microenvironment of pH-sensitive proteins at the intercalated disks (e.g., connexin 43) and near the cytosolic surface of sarcoplasmic reticulum cisternae (e.g., ryanodine receptor), thereby influencing impulse conduction and excitation-contraction coupling.

Dynamic plasma extracellular vesicle long RNA profiling changes during the peri-operative period

2020 ◽  
Author(s):  
qing hua ◽  
wenhao xu ◽  
xuefang shen ◽  
xi tian ◽  
Peng Wang ◽  
...  
Keyword(s):  
Immune Cell ◽  
Surgical Stress ◽  
Distant Metastases ◽  
Cell Types ◽  
R Package ◽  
Extracellular Vesicle ◽  
Differentially Expressed ◽  
Dynamic Changes ◽  
Rna Profiling ◽  
Time Points

Abstract Background: Surgery remains the most important treatment strategy for solid tumors, such as colorectal cancer (CRC); However, a number of studies have suggested that surgical stress contributes to tumor recurrence or distant metastases. Extracellular vesicles (EVs), which contain a rich variety of RNAs with specialized functions and clinical applications, have been shown to be an indicator for diagnosis and prognosis of cancers. The effect of surgical stress on the landscape and characteristics of EV long RNA (exLR) in human blood, however, remains largely unknown.Methods: We present an optimized strategy for exLR sequencing (exLR-seq) the plasma from three patients with CRC at 4 time points (before surgery [T0], after extubation [T1], 1 day after surgery [T2], and 3 days after surgery [T4]). The “Limma” R package was used to evaluate the dynamic changes of mRNAs and long non-coding (lnc)RNAs from EVs. We also constructed a protein–protein interaction (PPI) network of hub genes and predicted biological processes, cellular components, and molecular functions of gene ontology (GO) functional analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Results: We observed a sufficient number of exLRs, including 12,924 mRNAs and 2196 lncRNAs. Both mRNAs and lncRNAs underwent dynamic changes during the peri-operative period. Compared with T0, there were 110 mRNAs differentially expressed after extubation, 60 differentially expressed genes（DEGs）1 day after surgery, and 50 DEGs 3 days after surgery. A total of 11 genes changed at all 3 time points and were related to regulation of the membrane potential, receptor complex, and passive transmembrane transporter activity. In addition, 22 lncRNAs were differentially expressed after extubation (T1). Nineteen lncRNAs were differentially expressed between T0 and T2, and 38 lncRNAs were differentially expressed between T0 and T3. In addition, we found that only 3 lncRNAs changed at 3 time points. Interestingly, blood exLRs reflected the tissue origins and relative fractions of different immune cell types. EVs from CD8+ T，CD4+ memory T, and NK cells decreased after surgery and the absolute quality of EVs from immune cells decreased as well. Conclusion: In summary, this study demonstrated abundant exLRs in human plasma and the dynamic changes of these exLRs and exLRs originating from CD8+ T and CD4+ memory T cells were reduced during the peri-operative period.

scholarly journals Extracellular Vesicle as a Source of Alzheimer’s Biomarkers: Opportunities and Challenges

2019 ◽  
Vol 20 (7) ◽  
pp. 1728 ◽  
Author(s):  
Seongju Lee ◽  
Sakulrat Mankhong ◽  
Ju-Hee Kang
Keyword(s):  
Clinical Evidence ◽  
Biological Function ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Vital Role ◽  
Synaptic Loss ◽  
Memory Decline ◽  
Disease Propagation ◽  
The Central Nervous System ◽  
Yield And Purity

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease characterized by memory decline and cognitive dysfunction. Although the primary causes of AD are not clear, it is widely accepted that the accumulation of amyloid beta (Aβ) and consecutive hyper-phosphorylation of tau, synaptic loss, oxidative stress and neuronal death might play a vital role in AD pathogenesis. Recently, it has been widely suggested that extracellular vesicles (EVs), which are released from virtually all cell types, are a mediator in regulating AD pathogenesis. Clinical evidence for the diagnostic performance of EV-associated biomarkers, particularly exosome biomarkers in the blood, is also emerging. In this review, we briefly introduce the biological function of EVs in the central nervous system and discuss the roles of EVs in AD pathogenesis. In particular, the roles of EVs associated with autophagy and lysosomal degradation systems in AD proteinopathy and in disease propagation are discussed. Next, we summarize candidates for biochemical AD biomarkers in EVs, including proteins and miRNAs. The accumulating data brings hope that the application of EVs will be helpful for early diagnostics and the identification of new therapeutic targets for AD. However, at the same time, there are several challenges in developing valid EV biomarkers. We highlight considerations for the development of AD biomarkers from circulating EVs, which includes the standardization of pre-analytical sources of variability, yield and purity of isolated EVs and quantification of EV biomarkers. The development of valid EV AD biomarkers may be facilitated by collaboration between investigators and the industry.

scholarly journals Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model

2019 ◽  
Vol 11 (4) ◽  
pp. 776-788 ◽  
Author(s):  
Samantha E. Spellicy ◽  
Erin E. Kaiser ◽  
Michael M. Bowler ◽  
Brian J. Jurgielewicz ◽  
Robin L. Webb ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ischemic Stroke ◽  
Functional Outcome ◽  
Neural Stem Cell ◽  
Functional Outcomes ◽  
Extracellular Vesicle ◽  
Stroke Model ◽  
Midline Shift ◽  
Post Stroke ◽  
Non Invasive

AbstractMagnetic resonance imaging (MRI) is a clinically relevant non-invasive imaging tool commonly utilized to assess stroke progression in real time. This study investigated the utility of MRI as a predictive measure of clinical and functional outcomes when a stroke intervention is withheld or provided, in order to identify biomarkers for stroke functional outcome under these conditions. Fifteen MRI and ninety functional parameters were measured in a middle cerebral artery occlusion (MCAO) porcine ischemic stroke model. Multiparametric analysis of correlations between MRI measurements and functional outcome was conducted. Acute axial and coronal midline shift (MLS) at 24 h post-stroke were associated with decreased survival and recovery measured by modified Rankin scale (mRS) and were significantly correlated with 52 measured acute (day 1 post) and chronic (day 84 post) gait and behavior impairments in non-treated stroked animals. These results suggest that MLS may be an important non-invasive biomarker that can be used to predict patient outcomes and prognosis as well as guide therapeutic intervention and rehabilitation in non-treated animals and potentially human patients that do not receive interventional treatments. Neural stem cell–derived extracellular vesicle (NSC EV) was a disruptive therapy because NSC EV administration post-stroke disrupted MLS correlations observed in non-treated stroked animals. MLS was not associated with survival and functional outcomes in NSC EV–treated animals. In contrast to untreated animals, NSC EVs improved stroked animal outcomes regardless of MLS severity.

scholarly journals OOCHIP: Compartmentalized Microfluidic Perfusion System with Porous Barriers for Enhanced Cell–Cell Crosstalk in Organ-on-a-Chip

Micromachines ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 565
Author(s):  
Qasem Ramadan ◽  
Sajay Bhuvanendran Nair Gourikutty ◽  
Qingxin Zhang
Keyword(s):  
Drug Efficacy ◽  
Human Adipose Tissue ◽  
Cell Types ◽  
Cell Interaction ◽  
The Body ◽  
Close Proximity ◽  
Porous Barriers ◽  
Cell Cell

Improved in vitro models of human organs for predicting drug efficacy, interactions, and disease modelling are crucially needed to minimize the use of animal models, which inevitably display significant differences from the human disease state and metabolism. Inside the body, cells are organized either in direct contact or in close proximity to other cell types in a tightly controlled architecture that regulates tissue function. To emulate this cellular interface in vitro, an advanced cell culture system is required. In this paper, we describe a set of compartmentalized silicon-based microfluidic chips that enable co-culturing several types of cells in close proximity with enhanced cell–cell interaction. In vivo-like fluid flow into and/or from each compartment, as well as between adjacent compartments, is maintained by micro-engineered porous barriers. This porous structure provides a tool for mimicking the paracrine exchange between cells in the human body. As a demonstrating example, the microfluidic system was tested by culturing human adipose tissue that is infiltrated with immune cells to study the role if the interplay between the two cells in the context of type 2 diabetes. However, the system provides a platform technology for mimicking the structure and function of single- and multi-organ models, which could significantly narrow the gap between in vivo and in vitro conditions.

scholarly journals Measurement and standardization challenges for extracellular vesicle therapeutic delivery vectors

Nanomedicine ◽  
2020 ◽  
Vol 15 (22) ◽  
pp. 2149-2170
Author(s):  
Bryant C Nelson ◽  
Samantha Maragh ◽  
Ionita C Ghiran ◽  
Jennifer C Jones ◽  
Paul C DeRose ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Nucleic Acid ◽  
Lipid Bilayer ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Clinical Therapeutics ◽  
Measurement Systems ◽  
Therapeutic Delivery ◽  
Efficient Delivery ◽  
Standardized Measurement

Extracellular vesicles (EVs), such as exosomes and microvesicles, are nonreplicating lipid bilayer particles shed by most cell types which have the potential to revolutionize the development and efficient delivery of clinical therapeutics. This article provides an introduction to the landscape of EV-based vectors under development for the delivery of protein- and nucleic acid-based therapeutics. We highlight some of the most pressing measurement and standardization challenges that limit the translation of EVs to the clinic. Current challenges limiting development of EVs for drug delivery are the lack of: standardized cell-based platforms for the production of EV-based therapeutics; EV reference materials that allow researchers/manufacturers to validate EV measurements and standardized measurement systems for determining the molecular composition of EVs.

Sign in / Sign up

Export Citation Format

Share Document