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Exosome and Mesenchymal Stem cell

Fan Ye, Florence Herr, Amelia Vernochet, Benoit Menneson, Estelle Oberlin, Antoine Durrbach
Mesenchymal stem cells (MSCs) are powerful immunomodulators that regulate the diverse functions of immune cells involved in allogeneic reactions, such as T cells and natural killer cells (NK), through cell-cell contact or secreted factors. Exosomes secreted by MSCs may be involved in their regulatory functions, providing new therapeutic tools. Here, we showed that fetal liver (FL) MSC-derived exosomes inhibit proliferation, activation, and cytotoxicity of NK cells. Exosomes bearing LAP, TGFβ, and TSP1, a regulatory molecule for TGFβ, induced downstream TGFβ/Smad2/3 signaling in NK cells...
October 17, 2018: Stem Cells and Development
Bruna Codispoti, Massimo Marrelli, Francesco Paduano, Marco Tatullo
Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. In fact, MSCs can differentiate into several cell lineages and show paracrine behavior by releasing endogenous factors that stimulate tissue repair and modulate local immune response. Each MSC type is affected by specific biobanking issues-technical issues as well as regulatory and ethical concerns-thus making it quite tricky to safely and commonly use MSC banking for swift regenerative applications. Extracellular vesicles (EVs) include a group of 150⁻1000 nm vesicles that are released by budding from the plasma membrane into biological fluids and/or in the culture medium from varied and heterogenic cell types...
October 15, 2018: Journal of Clinical Medicine
Yubao Liu, Lupan Lin, Rui Zou, Chuanyang Wen, Zhen Wang, Fuqing Lin
Background Exosomes secreted by human mesenchymal stem cells (hMSCs) have been shown to promote cartilage regeneration. This study aimed to explore whether exosomal lncRNA-KLF3-AS1 derived from hMSCs can promote chondrocyte proliferation via miR-206/GIT1 axis in osteoarthritis (OA). Methods hMSCs and MSC-derived exosomes (MSC-exo) were prepared for morphological observation and identification by transmission electron microscopy (TEM) and flow cytometry. IL-1β-induced OA chondrocytes and collagenase-induced mouse OA model were established for the further experiments...
October 16, 2018: Cell Cycle
Ke Ren
Exosomes as a unique subtype of small extracellular vesicles (sEVs) have attracted increasing interest in recent years in the fields of mesenchymal stromal cell (MSC) research. Studies have confirmed that exosomes derived from MSCs preserve immunosuppressive phenotype and can mimic therapeutic benefits of their parent cells. This review briefly summarizes most recent findings on the potential of exosomes as an alternative of therapeutic MSCs, focusing on the role of MSCs and their secreted exosomes in regulation of immune cells, preclinical and clinical evidence of therapeutic outcomes of MSC exosomes, and the biodistribution and pharmacokinetic profile of systemically administered exosomes...
October 15, 2018: Odontology
Yu Fujita, Tsukasa Kadota, Jun Araya, Takahiro Ochiya, Kazuyoshi Kuwano
It is currently thought that extracellular vesicles (EVs), such as exosomes and microvesicles, play an important autocrine/paracrine role in intercellular communication. EVs package proteins, mRNA and microRNA (miRNA), which have the ability to transfer biological information to recipient cells in the lungs. Depending on their origin, EVs fulfil different functions. EVs derived from mesenchymal stem cells (MSCs) have been found to promote therapeutic activities that are comparable to MSCs themselves. Recent animal model-based studies suggest that MSC-derived EVs have significant potential as a novel alternative to whole-cell therapies...
October 14, 2018: Journal of Clinical Medicine
Senthilkumar Kalimuthu, Prakash Gangadaran, Ramya Lakshmi Rajendran, Liya Zhu, Ji Min Oh, Ho Won Lee, Arunnehru Gopal, Se Hwan Baek, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Exosomes derived from mesenchymal stem cells (MSCs) have been evaluated for their potential to be used as drug delivery vehicles. Synthetically personalized exosome mimetics (EMs) could be the alternative vesicles for drug delivery. In this study, we aimed to isolate EMs from human MSCs. Cells were mixed with paclitaxel (PTX) and PTX-loaded EMs (PTX-MSC-EMs) were isolated and evaluated for their anticancer effects against breast cancer. EMs were isolated from human bone marrow-derived MSCs. MSCs (4 × 106 cells/mL) were mixed with or without PTX at different concentrations in phosphate-buffered saline (PBS) and serially extruded through 10-, 5-, and 1-μm polycarbonate membrane filters using a mini-extruder...
2018: Frontiers in Pharmacology
Edwin E Reza-Zaldivar, Mercedes A Hernández-Sapiéns, Benito Minjarez, Yanet K Gutiérrez-Mercado, Ana L Márquez-Aguirre, Alejandro A Canales-Aguirre
Alzheimer's disease (AD) is the most common type of dementia affecting regions of the central nervous system that exhibit synaptic plasticity and are involved in higher brain functions such as learning and memory. AD is characterized by progressive cognitive dysfunction, memory loss and behavioral disturbances of synaptic plasticity and energy metabolism. Cell therapy has emerged as an alternative treatment of AD. The use of adult stem cells, such as neural stem cells and Mesenchymal Stem Cells (MSCs) from bone marrow and adipose tissue, have the potential to decrease cognitive deficits, possibly by reducing neuronal loss through blocking apoptosis, increasing neurogenesis, synaptogenesis and angiogenesis...
2018: Frontiers in Cellular Neuroscience
Nazli Jafarzadeh, Zohreh Safari, Majid Pornour, Naser Amirizadeh, Mehdi Forouzandeh Moghadam, Majid Sadeghizadeh
Leukemic cells can impact the bone marrow niche to create a tumor-favorable microenvironment using their secreted factors. Little knowledge is available about immunosuppressive and tumor-promoting properties of chronic myeloid leukemia derived exosomes in bone marrow stromal components. We report here that K562-derived exosomes can affect the gene expression, cytokine secretion, nitric oxide (NO) production, and redox potential of bone marrow mesenchymal stem cells (BM-MSCs) and macrophages. Human BM-MSCs and mouse macrophages were treated with K562-derived exosomes...
October 14, 2018: Journal of Cellular Physiology
Soo Kim, Seul Ki Lee, Hyunjung Kim, Tae Min Kim
Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) serve as a unique source for cell therapy. We investigated whether exosomes from iMSCs promote the proliferation of human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs). iPSCs were established from human Wharton's jelly MSCs and were allowed to differentiate into iMSCs. Exosomes were collected from the culture supernatant of MSCs (MSC-exo) and iMSCs (iMSC-exo), and their characteristics were investigated. Both exosome types possessed basic characteristics of exosomes and were taken up by skin cells in vitro and in vivo...
October 11, 2018: International Journal of Molecular Sciences
Ji-Gang He, Qiao-Li Xie, Bei-Bei Li, Liang Zhou, Dan Yan
BACKGROUND: The immunosuppressive activity of mesenchymal stem cells (MSCs) has been exploited to induce tolerance after organ transplantation. The indoleamine 2,3-dioxygenase (IDO) may have beneficial effects in the immunoregulatory properties of MSCs. It was recently revealed that exosomes derived from MSCs play important roles in mediating the biological functions of MSCs. This study aimed to explore the roles of exosomes derived from MSCs in the induction of immune tolerance. METHODS: Dendritic cells (DCs) and T-cells were cultured with exosomes derived from rat bone marrow MSCs (BMSCs) overexpressing IDO1 or controls...
October 12, 2018: Cell Transplantation
Su-Yan Bian, Hong-Bin Liu, Hong-Wei Liu, Qi-Wei Zhu
OBJECTIVE: To explore the proangiogenic activity of exsomes released by human umbilical cord mesenchymal stem cells (MSCs) stimulated by erythropoietin and platelet-derived growth factor BB (PDGF-BB). METHODS: Human umbilical cord-derived MSCs were seeded and maintained in culture overnight. The media were then replaced by alpha-MEM containing EPO (1 U/ml) and/or PDGF-BB (50 ng/ml), and the culture was maintained for 72 hours. The exosomes from the culture supernatants were isolated with a routine ultra-catrifagation method...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Ling Fang, Xue-Feng Shi, Hui-Yan Sun, Yu-Xiang Li, Feng-Jun Xiao, Hua Wang, Li-Sheng Wang
OBJECTIVE: To investigate the effects of exosomes derived from miR-486 gene-modified umbilical cord mesenchymal stem cells (UC-MSCs) on biological characteristics of rat cardiomyocytes. METHODS: The human umbilical cord mesenchymal stem cells (UC-MSCs) were isolated and cultured, then the immunophenotypes and ability of osteogenic and adipogenic differentiation of UC-MSC were identified. The structure of exosomes was observed by electron microscopy; the effect of exosomes on cell migration was detected by transwell cell migration test; the miR-486 high expression of UC-MSC was mediated by using recombinant adenovirus vector, moreover the UC-MSC with high expression of miR-486 were identified by qPT-PCR...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Hao Sun, Shu Hu, Ziji Zhang, Jiayong Lun, Weiming Liao, Zhiqi Zhang
The aim of the current study was to compare the expression of microRNAs (miRNAs) in exosomes derived from human bone mesenchymal stem cells (hBMSCs) with and without chondrogenic induction. Exosomes derived from hBMSCs were isolated and identified. Microarray analysis was performed to compare miRNA expression between exosomes derived from hBMSCs with and without chondrogenic induction, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the differentially expressed miRNAs. hBMSCs were transfected with miRNA mimic to extract miRNA-overexpressed exosomes...
September 11, 2018: Journal of Cellular Biochemistry
Chengwei Ju, Youngjun Li, Yan Shen, Yutao Liu, Jingwen Cai, Naifeng Liu, Gengshan Ma, Yaoliang Tang
We demonstrated the effects of exosomes secreted by cardiac mesenchymal stem cells (C-MSC-Exo) in protecting acute ischemic myocardium from reperfusion injury. To investigate the effect of exosomes from C-MSC on angiogenesis, we injected C-MSC-Exo or PBS intramuscularly into ischemic hind limb. Blood perfusion of limb was evaluated by laser Doppler Imaging. We observed that ischemic limb treated with C-MSC-Exo exhibits improved blood perfusion compared to ischemic limb treated with PBS at 2 weeks and 1 month after induction of limb ischemia...
October 1, 2018: Journal of Cardiovascular Translational Research
Jennifer Phan, Priyadarsini Kumar, Dake Hao, Kewa Gao, Diana Farmer, Aijun Wang
Through traditional medicine, there were diseases and disorders that previously remained untreated or were simply thought to be incurable. Since the discovery of mesenchymal stem cells (MSCs), there has been a flurry of research to develop MSC-based therapy for diseases and disorders. It is now well-known that MSCs do not typically engraft after transplantation and exhibit their therapeutic effect via a paracrine mechanism. In addition to secretory proteins, MSCs also produce extracellular vesicles (EVs), membrane-bound nanovesicles containing proteins, DNA and RNA...
2018: Journal of Extracellular Vesicles
Bethany N Hannafon, Wei-Qun Ding
microRNAs (miRNAs) are small RNAs that influence gene expression by targeting messenger RNAs (mRNAs). Depending on the function of their target genes, miRNAs may regulate the expression of oncogenes and tumor suppressors, thereby contributing to the promotion or inhibition of tumor progression. Ductal carcinoma in situ (DCIS), although often diagnosed as breast cancer, is a potential precursor to invasive ductal carcinoma. Many of the genetic events required for the invasive progression of DCIS occur at the pre-invasive stage, and these events include changes to the expression of miRNAs...
September 28, 2018: American Journal of Pathology
Teng Ma, Yueqiu Chen, Yihuan Chen, Qingyou Meng, Jiacheng Sun, Lianbo Shao, Yunsheng Yu, Haoyue Huang, Yanqiu Hu, Ziying Yang, Junjie Yang, Zhenya Shen
Background: To cure ischemic diseases, angiogenesis needs to be improved by various strategies in ischemic area. Considering that microRNA-132 (miR-132) regulates endothelial cell behavior during angiogenesis and the safe and efficacious delivery of microRNAs in vivo is rarely achieved, an ideal vehicle for miR-132 delivery could bring the promise for ischemic diseases. As a natural carrier of biological molecules, exosomes are more and more developed as an ideal vehicle for miRNA transfer...
2018: Stem Cells International
Tarek M K Motawi, Dina Sabry, Nadine W Maurice, Sherine M Rizk
BACKGROUND: Pre-eclampsia (PE) is one of the most threatening pregnancy complications. So far neither a secure, competent therapy for PE nor effective biomarkers for a premature discovery has been achieved. However, currently, the use of released microRNAs (miRNAs) as potential biomarkers and therapy targets for various diseases is the dominating area of research. The aim of our study was to identify miRNAs 136, 494 and 495 genes expression in exosomes of peripheral blood compared to umbilical cord mesenchymal stem cells (UCMSCs) conditioned media released exososomes in patients with PE, as valuable markers for PE early prediction...
September 25, 2018: Archives of Biochemistry and Biophysics
Mao Ding, Yang Shen, Ping Wang, Zhaohong Xie, Shunliang Xu, ZhengYu Zhu, Yun Wang, Yongtao Lyu, Dewei Wang, Linlin Xu, JianZhong Bi, Hui Yang
Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by excessive accumulation of the amyloid-β peptide (Aβ) in the brain, which has been considered to mediate the neuroinflammation process. Microglial activation is the main component of neuroimmunoregulation. In recent years, exosomes isolated from human umbilical cord mesenchymal stem cells (hucMSC-exosomes) have been demonstrated to mimic the therapeutic effects of hucMSCs in many inflammation-related diseases. In this study, exosomes from the supernatant of hucMSCs were injected into AD mouse models...
September 26, 2018: Neurochemical Research
Guping Mao, Ziji Zhang, Shu Hu, Zhiqi Zhang, Zongkun Chang, Zhiyu Huang, Weiming Liao, Yan Kang
BACKGROUND: WNT5A is known to be involved in the pathogenesis of osteoarthritis. This study investigated the molecular mechanism of exosomal miR-92a-3p and WNT5A in chondrogenesis and cartilage degeneration. METHODS: Exosomal miR-92a-3p expression was assessed in vitro in a human mesenchymal stem cell (MSC) model of chondrogenesis and in normal and OA primary human chondrocytes (PHCs). MSCs and PHCs were treated with exosomes derived from MSC-miR-92a-3p (MSC-miR-92a-3p-Exos) or its antisense inhibitor (MSC-anti-miR-92a-3p-Exos), respectively...
September 26, 2018: Stem Cell Research & Therapy
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