Mesenchymal stem/stromal cell extracellular vesicles: From active principle to next generation drug delivery system

Crivelli, Barbara; Chlapanidas, Theodora; Perteghella, Sara; Lucarelli, Enrico; Pascucci, Luisa; Brini, A.T.; Ferrero, Ivana; Marazzi, Mario; Pessina, Augusto; Torre, Maria Luisa

doi:10.1016/j.jconrel.2017.07.023

Cited by 124 publications

(81 citation statements)

References 230 publications

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“…The therapeutic potential of MSC-derived EV (MSC-EV) was shown in several experimental conditions like damaged bone marrow, renal, pulmonary and cardiovascular tissues (for review see (Akyurekli et al, 2015;Borger et al, 2017;Crivelli et al, 2017;Quesenberry et al, 2015;Sharma et al, 2017;Wang et al, 2017)).…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles derived from human embryonic stem cell‐MSCs ameliorate cirrhosis in thioacetamide‐induced chronic liver injury

Mardpour¹,

Hassani

Mardpour³

et al. 2018

Journal Cellular Physiology

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Various somatic tissue-derived mesenchymal stromal cells (MSCs) have been considered as an attractive therapeutic tool for treatment of liver diseases in which the secretion of soluble factors or extracellular vesicles (EVs) is the most probable mechanism. The experimental application of human embryonic stem cell-derived MSC (ES-MSC) increased rapidly and showed promising results, in vitro and in vivo. However, possible therapeutic effects of human ES-MSC and their EVs on Thioacetamide (TAA)-induced chronic liver injury have not been evaluated yet. Our data indicated that human ES-MSC can significantly suppress the proliferation of peripheral blood mononuclear cells compared to bone marrow (BM)-MSC and adipose (AD)-MSC. Moreover, ES-MSC increased the secretion of anti-inflammatory cytokines (i.e., TGF-β and IL-10) and decreased IFN-γ, compared to other MSCs. ES-MSC EVs demonstrated immunomodulatory activities comparable to parental cells and ameliorated cirrhosis in TAA-induced chronic rat liver injury, that is, reduction in fibrosis and collagen density, necrosis, caspase density, portal vein diameter, and transaminitis. The gene expression analyses also showed upregulation in collagenases (MMP9 and MMP13), anti-apoptotic gene (BCL-2) and anti-inflammatory cytokines (TGF-β1 and IL-10) and down-regulation of major contributors to fibrosis (Col1α, αSMA, and TIMP1), pro-apoptotic gene (BAX) and pro-inflammatory cytokines (TNFα and IL-2) following treatment with ES-MSC and ES-MSC-EV. These results demonstrated that human ES-MSC and ES-MSC EV as an off-the-shelf product, that needs further assessment to be suggested as an allogeneic product for therapeutic applications for liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Extracellular vesicles derived from human embryonic stem cell‐MSCs ameliorate cirrhosis in thioacetamide‐induced chronic liver injury

Mardpour¹,

Hassani

Mardpour³

et al. 2018

Journal Cellular Physiology

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“…drugs, proteins, RNA, etc.) into targeted MSC‐derived extracellular vesicles or exosomes via active or passive loading mechanisms . Despite these approaches, lung entrapment remains a critical challenge for MSC‐based drug delivery; although evidence suggests this is a surmountable engineering challenge.…”

Section: Msc Homing Mechanismsmentioning

confidence: 99%

Concise Review: Mesenchymal Stem Cell-Based Drug Delivery: The Good, the Bad, the Ugly, and the Promise

Krueger

Thorek

Denmeade

et al. 2018

Stem Cells Translational Medicine

205

163

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The development of mesenchymal stem cells (MSCs) as cell‐based drug delivery vectors for numerous clinical indications, including cancer, has significant promise. However, a considerable challenge for effective translation of these approaches is the limited tumor tropism and broad biodistribution observed using conventional MSCs, which raises concerns for toxicity to nontarget peripheral tissues (i.e., the bad). Consequently, there are a variety of synthetic engineering platforms in active development to improve tumor‐selective targeting via increased homing efficiency and/or specificity of drug activation, some of which are already being evaluated clinically (i.e., the good). Unfortunately, the lack of robust quantification and widespread adoption of standardized methodologies with high sensitivity and resolution has made accurate comparisons across studies difficult, which has significantly impeded progress (i.e., the ugly). Herein, we provide a concise review of active and passive MSC homing mechanisms and biodistribution postinfusion; in addition to in vivo cell tracking methodologies and strategies to enhance tumor targeting with a focus on MSC‐based drug delivery strategies for cancer therapy. Stem Cells Translational Medicine 2018;1–13

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“…huc-MSC-EVs have been shown to contain numerous functional proteins, mRNAs, and microRNAs that exert important roles in physiologic and pathologic conditions (47,48). To evaluate the underlying mechanisms, we analyzed the publicly available database.…”

Section: Mnsod In Huc-msc-evs Prevents Hepatocytes From Oxidative Strmentioning

confidence: 99%

Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia‐reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response

et al. 2018

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Mesenchymal stem cells (MSCs) have been reported to exert therapeutic effects on immunoregulation, tissue repair, and regeneration from the bench to the bedside. Increasing evidence demonstrates that extracellular vesicles (EVs) derived from MSCs could contribute to these effects and are considered as a potential replacement for stem cell‐based therapies. However, the efficacy and underlying mechanisms of EV‐based treatment in hepatic ischemia‐reperfusion injury (IRI) remain unclear. Here, we demonstrated that human umbilical cord MSC‐EVs (huc‐MSC‐EVs) could protect against IRI‐induced hepatic apoptosis by reducing the infiltration of neutrophils and alleviating oxidative stress in hepatic tissue in vivo. Meanwhile, huc‐MSC‐EVs reduced the respiratory burst of neutrophils and prevented hepatocytes from oxidative stress‐induced cell death in vitro. Interestingly, we found that the mitochondria‐located antioxidant enzyme, manganese superoxide dismutase (MnSOD), was encapsulated in huc‐MSC‐EVs and reduced oxidative stress in the hepatic IRI model. Knockdown of MnSOD in huc‐MSCs decreased the level of MnSOD in huc‐MSC‐EVs and attenuated the antiapoptotic and antioxidant capacities of huc‐MSC‐EVs, which could be partially rescued by MnSOD mimetic manganese (III) 5,10,15,20‐tetrakis (4‐benzoic acid) porphyrin (MnTBAP). In summary, these findings provide new clues to reveal the therapeutic effects of huc‐MSC‐EVs on hepatic IRI and evaluate their preclinical application.—Yao, J., Zheng, J., Cai, J., Zeng, K., Zhou, C., Zhang, J., Li, S., Li, H., Chen, L., He, L., Chen, H., Fu, H., Zhang, Q., Chen, G., Yang, Y., Zhang, Y. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia‐reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response. FASEB J. 33, 1695–1710 (2019). http://www.fasebj.org

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Mesenchymal stem/stromal cell extracellular vesicles: From active principle to next generation drug delivery system

Cited by 124 publications

References 230 publications

Extracellular vesicles derived from human embryonic stem cell‐MSCs ameliorate cirrhosis in thioacetamide‐induced chronic liver injury

Extracellular vesicles derived from human embryonic stem cell‐MSCs ameliorate cirrhosis in thioacetamide‐induced chronic liver injury

Concise Review: Mesenchymal Stem Cell-Based Drug Delivery: The Good, the Bad, the Ugly, and the Promise

Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia‐reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response

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