The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration

Konala, Vijay Bhaskar Reddy; Mamidi, Murali Krishna; Bhonde, Ramesh; Das, Anjan Kumar; Pochampally, Radhika; Pal, Rajarshi

doi:10.1016/j.jcyt.2015.10.008

Cited by 371 publications

(296 citation statements)

References 82 publications

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“…Considering that exosome-like vesicles are completely cell-free and not highly immunogenic, exosome-like vesicles could be an important tool for use during adipose tissue engineering (Konala et al, 2016). Therefore, further research is needed to study the possibility that exosome-like vesicles act as a proadipogenic factor to enable use during adipose tissue engineering.…”

Section: Discussionmentioning

confidence: 99%

miR-450a-5p within rat adipose tissue exosome-like vesicles promotes adipogenic differentiation by targeting WISP2

Zhang

Dai

et al. 2017

Journal of Cell Science

103

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Adipose tissue is an active endocrine organ that can secrete a wide number of factors to regulate adipogenesis via paracrine signals. In addition to soluble proteins in adipose tissue, microRNAs (miRNAs) enriched in extracellular vesicles (EVs), such as exosomes or microvesicles, could modulate intercellular communications. In this study, we demonstrated that exosome-like vesicles derived from adipose tissue (Exo-AT) were internalized by adipose tissue-derived stem cells (ADSCs), and that these, in turn, induced adipogenesis. High-throughput sequencing showed that 45 miRNAs were enriched in Exo-AT, and 31.11% of them were associated with adipogenesis, compared with ADSC-derived exosome-like vesicles (Exo-ADSC). miR-450a-5p, one of the most abundant miRNAs in Exo-AT, was a proadipogenic miRNA. Further study demonstrated that miR-450a-5p promoted adipogenesis through repressing expression of WISP2 by targeting its 3′ untranslated region. Additionally, Exo-AT could also downregulate the expression of WISP2, while miR-450a-5p inhibitor reversed this effect. Moreover, inhibition of miR-450a-5p impaired adipogenesis mediated by exosome-like vesicles. In conclusion, Exo-AT mediates adipogenic differentiation through a mechanism involving transfer of miR-450a-5p.

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Section: Discussionmentioning

confidence: 99%

miR-450a-5p within rat adipose tissue exosome-like vesicles promotes adipogenic differentiation by targeting WISP2

Zhang

Dai

et al. 2017

Journal of Cell Science

103

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“…There is growing evidence that extracellular vesicles (EVs) released by MSCs contribute to the therapeutic repertoire of the trophic factors of MSCs [66,67]. Application of MSC-derived EVs has shown efficacy in various animal models such as myocardial infarction, limb ischemia, wound healing, or kidney, liver and lung injury [68,69].…”

Section: Mscs Secrete Trophic Factors and Produce Extracellular Vesiclesmentioning

confidence: 99%

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy

Schäfer

Spohn

Baer

2016

Transfus Med Hemother

107

126

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Mesenchymal stem/stromal cells (MSCs) are becoming increasingly important for the development of cell therapeutics in regenerative medicine. Featuring immunomodulatory potential as well as secreting a variety of trophic factors, MSCs showed remarkable therapeutic effects in numerous preclinical disease models. However, sustainable translation of MSC therapies to the clinic is hampered by heterogeneity of MSCs and non-standardized in vitro culture technologies. Moreover, potent MSC therapeutics require MSCs with maximum regenerative capacity. There is growing evidence that in vitro preconditioning strategies of MSCs can optimize their therapeutic potential. In the following we will discuss achievements and challenges of the development of MSC therapies in regenerative medicine highlighting specific in vitro preconditioning strategies prior to cell transplantation to increase their therapeutic efficacy.

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“…Studies have revealed many functions mediated by this type of cell, such as reducing inflammation, modulating immune responses, promoting tissue regeneration, and inhibiting tumor progression [7][8][9]. In addition, MSC treatment has been the focus of more than 560 clinical trials that supply exogenous or activate endogenous MSCs [10] and has become the most effective source of cell-based therapy [11,12]. Human umbilical cord MSCs (uMSCs) are a kind of MSC derived from umbilical cord through a noninvasive procedure, allowing robust in vitro culture expansion, and its physiological properties could be basically reserved under cryostorage [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Exosomal MicroRNAs Derived From Umbilical Mesenchymal Stem Cells Inhibit Hepatitis C Virus Infection

Qian

Fang

et al. 2016

Stem Cells Translational Medicine

139

116

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Hepatitis C virus (HCV) is a significant global public health problem, causing more than 350,000 deaths every year. Although the development of direct-acting antivirals has improved the sustained virological response rate in HCV patients, novel anti-HCV agents with higher efficacy as well as better tolerance and cheaper production costs are still urgently needed. Cell-based therapy, especially its unique and strong paracrine ability to transfer information to other cells via extracellular vesicles such as exosomes, has become one of the most popular therapeutic methods in recent years. In our study, exosomes secreted from umbilical mesenchymal stem cells (uMSCs), which are widely used in regenerative medicine, inhibited HCV infection in vitro, especially viral replication, with low cell toxicity. Our analysis revealed that microRNAs (miRNAs) from uMSC-derived exosomes (uMSC-Exo) had their unique expression profiles, and these functional miRNAs, mainly represented by let-7f, miR-145, miR-199a, and miR-221 released from uMSC-Exo, largely contributed to the suppression of HCV RNA replication. These four miRNAs possessed binding sites in HCV RNA as demonstrated by the target prediction algorithm. In addition, uMSC-Exo therapy showed synergistic effect when combined with U.S. Food and Drug Administration-approved interferon-a or telaprevir, enhancing their anti-HCV ability and thus improving the clinical significance of these regenerative substances for future application as optimal adjuvants of anti-HCV therapy. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1190-1203 SIGNIFICANCEThis work reported, for the first time, the identification of stem cell-derived exosomes of antiviral activity. Umbilical mesenchymal stem cell-secreted exosomes inhibited hepatitis C virus infection through transporting a mixture of microRNAs complementing the viral genomes to the host cells. This finding provides insights and prospects for physiologically secreted substances for antiviral therapy.

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The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration

Cited by 371 publications

References 82 publications

miR-450a-5p within rat adipose tissue exosome-like vesicles promotes adipogenic differentiation by targeting WISP2

miR-450a-5p within rat adipose tissue exosome-like vesicles promotes adipogenic differentiation by targeting WISP2

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy

Exosomal MicroRNAs Derived From Umbilical Mesenchymal Stem Cells Inhibit Hepatitis C Virus Infection

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