scholarly journals Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy

2021 ◽  
Vol 22 (20) ◽  
pp. 11035
Author(s):  
Virinder Kaur Sarhadi ◽  
Ravindra Daddali ◽  
Riitta Seppänen-Kaijansinkko
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Poor Prognosis ◽  
Paracrine Signaling ◽  
Mediated Communication ◽  
Multipotent Stem Cells ◽  
Genetic Complexity ◽  
Potential Applications

Osteosarcoma (OS) is an aggressive bone tumor that mainly affects children and adolescents. OS has a strong tendency to relapse and metastasize, resulting in poor prognosis and survival. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic targets. Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into adipocytes, osteoblasts, or chondroblasts. OS is thought to originate at some stage in the differentiation process of MSC to pre-osteoblast or from osteoblast precursors. MSCs contribute to OS progression by interacting with tumor cells via paracrine signaling and affect tumor cell proliferation, invasion, angiogenesis, immune response, and metastasis. Extracellular vesicles (EVs), secreted by OS cells and MSCs in the tumor microenvironment, are crucial mediators of intercellular communication, driving OS progression by transferring miRNAs/RNA and proteins to other cells. MSC-derived EVs have both pro-tumor and anti-tumor effects on OS progression. MSC-EVs can be also engineered to deliver anti-tumor cargo to the tumor site, which offers potential applications in MSC-EV-based OS treatment. In this review, we highlight the role of MSCs in OS, with a focus on EV-mediated communication between OS cells and MSCs and their role in OS pathogenesis and therapy.

scholarly journals Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

2021 ◽  
Vol 22 (3) ◽  
pp. 1375
Author(s):  
María Carmen Carceller ◽  
María Isabel Guillén ◽  
María Luisa Gil ◽  
María José Alcaraz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Nuclear Factor Κb ◽  
Peritoneal Macrophages ◽  
Toll Like Receptor 4 ◽  
Anti Inflammatory ◽  
Phagocytic Response

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

Isolation and Characterization of Mesenchymal Stem Cells from Chicken Liver

2020 ◽  
Vol 10 (1) ◽  
pp. 8-16
Author(s):  
Xibin Liu ◽  
Shuang Zhang ◽  
Weijun Guan ◽  
Dong Zheng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Markers ◽  
Multilineage Differentiation ◽  
Rt Pcr ◽  
Multipotent Stem Cells ◽  
Isolation And Characterization ◽  
Potential Applications ◽  
Polymerase Chain

Hepatic mesenchymal stem cells (HMSCs) are multipotent stem cells that is a vital part of the regeneration of hepatocytes after injury. In this study, HMSCs were isolated in embryonic livers from of 12-day-old chick embryo using collagenase, and the primary HMSCs were sub-cultured to passage. The protein markers of HMSCs, namely CD71, CD29 and CD44, were tested with immunofluorescence and Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The proliferation of HMSCs in different passages was detected using growth curve, which shown a typically sigmoidal. And then, the pluripotent of HMSCs was analyzed, the results showed that HMSCs could directly induce to differentiate into neural-like cells, adipocytes, and osteoblasts. Our data illustrated that the chick HMSCs have same characteristics to those obtained from other species. The capacity of these cells for multilineage differentiation shows promise for many potential applications.

Anti-inflammatory Effects of Mesenchymal Stem Cells and Their Secretomes in Pneumonia

2021 ◽  
Vol 22 ◽  
Author(s):  
Kamal Hezam ◽  
Rigen Mo ◽  
Chen Wang ◽  
Yue Liu ◽  
Zongjin Li
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Clinical Settings ◽  
Multipotent Progenitor Cells ◽  
Novel Coronavirus ◽  
The Cost ◽  
And Storage ◽  
Potential Therapeutics

: Mesenchymal stem cells (MSCs) are multipotent progenitor cells that play crucial roles in the microenvironment of injured tissues. The potential therapeutics of MSCs have attracted extensive attention for several diseases such as acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19) pneumonia. MSC-extracellular vesicles have been isolated from MSC-conditioned media (MSC-CM) with similar functional effects as parent MSCs. The therapeutic role of MSCs can be achieved through the balance between the inflammatory and regenerative microenvironments. Clinical settings of MSCs and their extracellular vesicles remain promising for many diseases, such as ARDS and pneumonia. However, their clinical applications remain limited due to the cost of growing and storage facilities of MSCs with a lack of standardized MSC-CM. This review highlights the proposed role of MSCs in pulmonary diseases and discusses the recent advances of MSC application for pneumonia and other lung disorders.

scholarly journals RSP5 Positively Regulates the Osteogenic Differentiation of Mesenchymal Stem Cells by Activating the K63-Linked Ubiquitination of Akt

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Changxiang Liang ◽  
Guoyan Liang ◽  
Xiaoqing Zheng ◽  
Yongxiong Huang ◽  
Shuaihao Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Repair ◽  
Multipotent Stem Cells ◽  
Cell Therapies ◽  
Ubiquitin Protein Ligase ◽  
Promising Target ◽  
Further Development

Mesenchymal stem cells (MSCs) are multipotent stem cells that have a strong osteogenic differentiation capacity. However, the molecular mechanism underlying the osteogenic differentiation of MSCs remains largely unknown and thus hinders further development of MSC-based cell therapies for bone repair in the clinic. RSP5, also called NEDD4L (NEDD4-like E3 ubiquitin protein ligase), belongs to the HECT (homologous to E6-AP carboxyl terminus) domain-containing E3 ligase family. Nevertheless, although many studies have been conducted to elucidate the role of RSP5 in various biological processes, its effect on osteogenesis remains elusive. In this study, we demonstrated that the expression of RSP5 was elevated during the osteogenesis of MSCs and positively regulated the osteogenic capacity of MSCs by inducing K63-linked polyubiquitination and activation of the Akt pathway. Taken together, our findings suggest that RSP5 may be a promising target to improve therapeutic efficiency by using MSCs for bone regeneration and repair.

scholarly journals Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
R. A. Contreras ◽  
F. E. Figueroa ◽  
F. Djouad ◽  
P. Luz-Crawford
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Multipotent Stem Cells ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Adaptive Immune Systems

Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studiedin vitroandin vivoin experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression.

scholarly journals Extracellular Vesicles from Mesenchymal Stem Cells as Potential Treatments for Osteoarthritis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1287
Author(s):  
Nur Azira Mohd Noor ◽  
Asma Abdullah Nurul ◽  
Muhammad Rajaei Ahmad Mohd Zain ◽  
Wan Khairunnisaa Wan Nor Aduni ◽  
Maryam Azlan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Cartilage Regeneration ◽  
Target Cells ◽  
Inflammatory Drugs ◽  
Degenerative Disorder ◽  
Intercellular Communications

Osteoarthritis (OA) is a chronic degenerative disorder of the joint and its prevalence and severity is increasing owing to ageing of the population. Osteoarthritis is characterized by the degradation of articular cartilage and remodeling of the underlying bone. There is little understanding of the cellular and molecular processes involved in pathophysiology of OA. Currently the treatment for OA is limited to painkillers and anti-inflammatory drugs, which only treat the symptoms. Some patients may also undergo surgical procedures to replace the damaged joints. Extracellular vesicles (EV) play an important role in intercellular communications and their concentration is elevated in the joints of OA patients, although their mechanism is unclear. Extracellular vesicles are naturally released by cells and they carry their origin cell information to be delivered to target cells. On the other hand, mesenchymal stem cells (MSCs) are highly proliferative and have a great potential in cartilage regeneration. In this review, we provide an overview of the current OA treatments and their limitations. We also discuss the role of EV in OA pathophysiology. Finally, we highlight the therapeutic potential of MSC-derived EV in OA and their challenges.

scholarly journals Upregulation of Extracellular Vesicles-Encapsulated miR-132 Released From Mesenchymal Stem Cells Attenuates Ischemic Neuronal Injury by Inhibiting Smad2/c-jun Pathway via Acvr2b Suppression

2021 ◽  
Vol 8 ◽  
Author(s):  
Bin Feng ◽  
Lei Meng ◽  
Liming Luan ◽  
Zhihao Fang ◽  
Peng Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Neuronal Cell ◽  
Neuronal Injury ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Ischemic Neuronal Injury

Ischemic cerebrovascular disease is a significant and common public health issue worldwide. The emerging roles of mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) in ischemic neuronal injury continue to be investigated. The current study aimed to investigate the role of EV-derived miR-132 from MSCs in ischemic neuronal injury. EVs were initially isolated from bone MSCs (BMSCs) and subsequently evaluated. A middle cerebral artery occlusion (MCAO) mouse model was constructed with the neurological function evaluated through a series of neurological scores, a pole test, and a foot fault test. Histopathological changes, neuron viability, and apoptosis, as well as cerebral infarction, were detected by hematoxylin and eosin (HE) staining and 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining. The targeting relationship between microRNA (miR)-132 and Activin receptor type IIB (Acvr2b) was further confirmed based on dual-luciferase reporter gene assay results. Loss- and gain-of-function assays were conducted to elucidate the role of miR-132, EV-derived miR-132, Acvr2b, and Smad2 in oxygen-glucose deprivation (OGD)-treated neurons, and in mice models. Neuronal cell viability and apoptosis were evaluated via Cell Counting kit-8 (CCK-8) and flow cytometry. Our results indicated that Acvr2b was highly expressed, while miR-132 was poorly expressed in the MCAO mice and OGD-treated neurons. Acvr2b silencing or upregulation of miR-132 led to an elevation in neuronal activity, decreased neuronal apoptosis, reduced expression of Bax, and cleaved-caspase 3, as well as increased Bcl-2 expression. Acvr2b expression was targeted and inhibited by miR-132. EV-derived Acvr2b promoted activation of phosphorylated-Smad2 (p-Smad2)/c-jun signaling pathway, ultimately inducing neuronal injury. Our study provides evidence demonstrating that the overexpression of c-jun inhibits the protective role of MSCs-derived EV-miR-132 in neuronal injury. Upregulation of EV-derived miR-132 released from MSCs attenuates ischemic neuronal injury by inhibiting Smad2/c-jun pathways via the suppression of Acvr2b.

scholarly journals Insights into the Secretome of Mesenchymal Stem Cells and Its Potential Applications

2019 ◽  
Vol 20 (18) ◽  
pp. 4597 ◽  
Author(s):  
Sharon Eleuteri ◽  
Alessandra Fierabracci
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Response ◽  
Diagnostic Procedures ◽  
Clinical Applications ◽  
Potential Applications

Mesenchymal stem cells (MSCs) have regenerative, immunoregulatory properties and can be easily isolated and expanded in vitro. Despite being a powerful tool for clinical applications, they present limitations in terms of delivery, safety, and variability of therapeutic response. Interestingly, the MSC secretome composed by cytokines, chemokines, growth factors, proteins, and extracellular vesicles, could represent a valid alternative to their use. It is noteworthy that MSC-derived extracellular vesicles (MSC-EVs) have the same effect and could be advantageous compared to the parental cells because of their specific miRNAs load. MiRNAs could be useful both in diagnostic procedures such as “liquid biopsy” to identify early pathologies and in the therapeutic field. Not only are MSC-EVs’ preservation, transfer, and production easier, but their administration is also safer, hence some clinical trials are ongoing. However, much effort is required to improve the characterization of EVs to avoid artifacts and guarantee reproducibility of the studies.

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tissue Regeneration

2020 ◽  
Vol 29 ◽  
pp. 096368972090850 ◽  
Author(s):  
Bocheng Zhang ◽  
Xiaoyuan Tian ◽  
Jun Hao ◽  
Gang Xu ◽  
Weiguo Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Tissue Repair ◽  
Membrane Structure ◽  
Therapeutic Potential ◽  
Biological Functions ◽  
Self Renewal ◽  
Multipotent Stem Cells

Mesenchymal stem cells (MSCs) are multipotent stem cells that have attracted increasing interest in the field of regenerative medicine. Previously, the differentiation ability of MSCs was believed to be primarily responsible for tissue repair. Recent studies have shown that paracrine mechanisms play an important role in this process. MSCs can secrete soluble molecules and extracellular vesicles (EVs), which mediate paracrine communication. EVs contain large amounts of proteins and nucleic acids, such as mRNAs and microRNAs (miRNAs), and can transfer the cargo between cells. The cargoes are similar to those in MSCs and are not susceptible to degradation due to the protection of the EV bimolecular membrane structure. MSC-EVs can mimic the biological characteristics of MSCs, such as differentiation, maturation, and self-renewal. Due to their broad biological functions and their ability to transfer molecules between cells, EVs have been intensively studied by an increasing number of researchers with a focus on therapeutic applications, especially those of EVs secreted by MSCs. In this review, we discuss MSC-derived EVs and their therapeutic potential in tissue regeneration.

scholarly journals Detection of MicroRNAs in Extracellular Vesicles Secreted by Umbilical Cord-derived Mesenchymal Stem Cells

2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Nguyen Thu Huyen ◽  
Duong Minh Chau ◽  
Do Thi Xuan Phuong ◽  
Nguyen Thanh Liem ◽  
Than Thi Trang Uyen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Potential Role ◽  
Culture Media ◽  
Therapeutic Effects ◽  
Potential Candidate ◽  
Disease Treatment

Extracellular vesicles (EVs) are emerging as a potential candidate for disease treatment due to their bioactive cargoes. Recently, mesenchymal stem cells (MSC)-derived EVs have shown their capacity to replace parental cells as their similar functions to MSCs. The therapeutic effects of EVs depend on their cargo, such as DNA, miRNA, proteins, and lipids. In this study, we expanded umbilical cord-derived MSCs (UCMSCs) for EV release. Additionally, we evaluated the expression level of several microRNAs in three EV populations, including apoptotic bodies (AB), microvesicles (MV), and exosomes (EX). Results showed that UCMSCs released three EV types: AB, MV, and EX into culture media. The three EV populations were different in morphology and size. Three EVs were detected to carry microRNAs, such as hsa-miR-320, hsa-miR-181b, and hsa-miR-140. Among these microRNAs, hsa-miR-140 expressed with the greatest level, followed by hsa-miR-181b and hsa-miR-320. The results of this study provide more knowledge about UCMSC-derived EV miRNAs in addition to reveal the potential role of UCMSC-EVs associated with detected miRNAs.

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