Exosomes as agents of change in the cardiovascular system

Poe, Adam J.; Knowlton, Anne A

doi:10.1016/j.yjmcc.2017.08.002

Cited by 37 publications

(34 citation statements)

References 129 publications

(169 reference statements)

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“…Tissue-engineered cartilage grafts have emerged as a promising alternative to overcome these problems and satisfy the ever-increasing clinical need [ 54 – 56 ]. Currently, exosomes have been identified as the principal agent in mediating the therapeutic efficacy of the cell-based regenerative medicine approach [ 20 , 21 , 57 , 58 ], and BMSC-Exos have been reported for promoting in situ cartilage defect repair [ 21 , 26 ]. However, the therapeutic outcome for subcutaneous cartilage defect repair is still limited because of the lack of a suitable pro-chondrogenic environment [ 17 , 40 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from mature chondrocytes facilitate subcutaneous stable ectopic chondrogenesis of cartilage progenitor cells

et al. 2018

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BackgroundDeveloping cartilage constructed with the appropriate matrix composition and persistent chondrogenesis remains an enduring challenge in cartilage defects. Cartilage progenitor cell (CPC)-based tissue engineering has attracted recent attention because of its strong chondrogenic differentiation capacity. However, due to the lack of a suitable chondrogenic niche, the clinical application of CPC-regenerated cartilage in the subcutaneous environment remains a challenge. In this study, exosomes derived from chondrocytes (CC-Exos) were used to provide the CPC constructs with a cartilage signal in subcutaneous environments for efficient ectopic cartilage regeneration.MethodsRabbit CPC-alginate constructs were prepared and implanted subcutaneously in nude mice. CC-Exos were injected into the constructs at the same dose (30 μg exosomes per 100 μL injection) after surgery and thereafter weekly for a period of 12 weeks. Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) were used as the positive control. The mice in the negative control were administered with the same volume of PBS. At 4 and 12 weeks after implantation, the potential of CC-Exos and BMSC-Exos to promote chondrogenesis and stability of cartilage tissue in a subcutaneous environment were analyzed by histology, immunostaining, and protein analysis. The influences of BMSC-Exos and CC-Exos on chondrogenesis and angiogenic characteristics in vitro were assessed via coculturing with CPCs and human umbilical vein endothelial cells.ResultsThe CC-Exos injection increased collagen deposition and minimized vascular ingrowth in engineered constructs, which efficiently and reproducibly developed into cartilage. The generated cartilage was phenotypically stable with minimal hypertrophy and vessel ingrowth up to 12 weeks, while the cartilage formed with BMSC-Exos was characterized by hypertrophic differentiation accompanied by vascular ingrowth. In vitro experiments indicated that CC-Exos stimulated CPCs proliferation and increased expression of chondrogenesis markers while inhibiting angiogenesis.ConclusionsThese findings suggest that the novel CC-Exos provides the preferable niche in directing stable ectopic chondrogenesis of CPCs. The use of CC-Exos may represent an off-the-shelf and cell-free therapeutic approach for promoting cartilage regeneration in the subcutaneous environment.

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Section: Discussionmentioning

confidence: 99%

Exosomes derived from mature chondrocytes facilitate subcutaneous stable ectopic chondrogenesis of cartilage progenitor cells

et al. 2018

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“…Interestingly, and consistent with membrane dysfunction, T2DM abolishes the cardioprotective potential of human and rat exosomes [ 15 ]. Exosomes are ~ 100 nm lipid bilayer vesicle derivatives of endosomes that play a role in transmitting protective signals between cells and tissues [ 152 ]. Cardioprotection may involve exosomal HSP70-dependent activation of myocyte toll like receptor 4 and reperfusion injury salvage kinase (RISK) signaling [ 153 ].…”

Section: Diabetes Impacts Myocardial Ischemic Tolerance and Cardiopromentioning

confidence: 99%

Myocyte membrane and microdomain modifications in diabetes: determinants of ischemic tolerance and cardioprotection

Russell

Toit

Peart

et al. 2017

Cardiovasc Diabetol

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Cardiovascular disease, predominantly ischemic heart disease (IHD), is the leading cause of death in diabetes mellitus (DM). In addition to eliciting cardiomyopathy, DM induces a ‘wicked triumvirate’: (i) increasing the risk and incidence of IHD and myocardial ischemia; (ii) decreasing myocardial tolerance to ischemia–reperfusion (I–R) injury; and (iii) inhibiting or eliminating responses to cardioprotective stimuli. Changes in ischemic tolerance and cardioprotective signaling may contribute to substantially higher mortality and morbidity following ischemic insult in DM patients. Among the diverse mechanisms implicated in diabetic impairment of ischemic tolerance and cardioprotection, changes in sarcolemmal makeup may play an overarching role and are considered in detail in the current review. Observations predominantly in animal models reveal DM-dependent changes in membrane lipid composition (cholesterol and triglyceride accumulation, fatty acid saturation vs. reduced desaturation, phospholipid remodeling) that contribute to modulation of caveolar domains, gap junctions and T-tubules. These modifications influence sarcolemmal biophysical properties, receptor and phospholipid signaling, ion channel and transporter functions, contributing to contractile and electrophysiological dysfunction, cardiomyopathy, ischemic intolerance and suppression of protective signaling. A better understanding of these sarcolemmal abnormalities in types I and II DM (T1DM, T2DM) can inform approaches to limiting cardiomyopathy, associated IHD and their consequences. Key knowledge gaps include details of sarcolemmal changes in models of T2DM, temporal patterns of lipid, microdomain and T-tubule changes during disease development, and the precise impacts of these diverse sarcolemmal modifications. Importantly, exercise, dietary, pharmacological and gene approaches have potential for improving sarcolemmal makeup, and thus myocyte function and stress-resistance in this ubiquitous metabolic disorder.

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“…Depending on their informational content, exosomes have the potential to modify cellular behaviour, promoting tumour progression, immune modulation, tissue regeneration and degeneration. Emerging evidence indicates that cardiac function, as well as cancer growth and progression, may rely on specific instructions delivered by exosomes (Poe & Knowlton, 2017;Xu et al 2017;Bollini et al 2018).…”

Section: Future Directionsmentioning

confidence: 99%

Mechanisms underlying the cross‐talk between heart and cancer

Brancaccio

Pirozzi

Hirsch

et al. 2019

The Journal of Physiology

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Cardiovascular diseases and cancer remain the leading cause of death worldwide. Despite the fact that these two conditions have long been considered as distinct clinical entities, recent epidemiological and experimental studies suggest that they should be contemplated and treated as co-morbidities. Heart failure represents nowadays a well-established complication of cancer, primarily as a consequence of the aggressive use of cardiotoxic anti-cancer treatments. On the other hand, the provocative idea that heart failure can prime carcinogenesis has started to emerge, though the molecular basis is still to be fully elucidated. This review summarizes the current knowledge on the mechanisms underlying the bidirectional communication between the failing heart and the cancer. We will discuss and/or speculate on the role of molecular mediators released by either the tumour or the heart that can potentially link heart failure and cancer.

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Exosomes as agents of change in the cardiovascular system

Cited by 37 publications

References 129 publications

Exosomes derived from mature chondrocytes facilitate subcutaneous stable ectopic chondrogenesis of cartilage progenitor cells

Exosomes derived from mature chondrocytes facilitate subcutaneous stable ectopic chondrogenesis of cartilage progenitor cells

Myocyte membrane and microdomain modifications in diabetes: determinants of ischemic tolerance and cardioprotection

Mechanisms underlying the cross‐talk between heart and cancer

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