Matrix-Bound Nanovesicles: The Effects of Isolation Method upon Yield, Purity, and Function

Quijano, Lina M.; Naranjo, Juan Diego; El-Mossier, Salma O.; Turner, Neill J.; Molina, Catalina Pineda; Bartolacci, Joseph; Zhang, Li; White, Lisa J.; Li, Hui; Badylak, Stephen F.

doi:10.1089/ten.tec.2020.0243

Cited by 19 publications

(38 citation statements)

References 84 publications

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“…MBVs, vesicles integrated within the dense fibrillar network of the ECM [ 200 ], are differ from exosomes in membrane composition and luminal cargo [ 204 ]. MBVs are supposed to have a potential role in development, homeostasis, wound healing, tissue regeneration and neoplasia [ 205 ], but to date, there is no information on their involvement in cancer.…”

Section: Ecm Remodeling and Modification In Cancermentioning

confidence: 99%

The Functional Role of Extracellular Matrix Proteins in Cancer

Popova

Jücker

2022

Cancers

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The extracellular matrix (ECM) is highly dynamic as it is constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM is a major structural component of the tumor microenvironment, and cancer development and progression require its extensive reorganization. Cancerized ECM is biochemically different in its composition and is stiffer compared to normal ECM. The abnormal ECM affects cancer progression by directly promoting cell proliferation, survival, migration and differentiation. The restructured extracellular matrix and its degradation fragments (matrikines) also modulate the signaling cascades mediated by the interaction with cell-surface receptors, deregulate the stromal cell behavior and lead to emergence of an oncogenic microenvironment. Here, we summarize the current state of understanding how the composition and structure of ECM changes during cancer progression. We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells.

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Section: Ecm Remodeling and Modification In Cancermentioning

confidence: 99%

The Functional Role of Extracellular Matrix Proteins in Cancer

Popova

Jücker

2022

Cancers

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“…All such approaches have shown pre-clinical efficacy in RA through immunomodulation of innate and adaptive immune cell populations 67 – 72 . MBV, a distinct population of extracellular vesicles, represent an alternative to these fluid-phase exosome therapies with minimal processing and manipulation in comparison 20 , 73 .…”

Section: Discussionmentioning

confidence: 99%

“…Urinary bladder ECM (UB-ECM) was prepared from market-weight pigs as previously described 9 , 73 . Porcine urinary bladders from market-weight animals (approximately 240 lbs.)…”

Section: Methodsmentioning

confidence: 99%

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Immunomodulatory matrix-bound nanovesicles mitigate acute and chronic pristane-induced rheumatoid arthritis

et al. 2022

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and destruction of synovial joints affecting ~7.5 million people worldwide. Disease pathology is driven by an imbalance in the ratio of pro-inflammatory vs. anti-inflammatory immune cells, especially macrophages. Modulation of macrophage phenotype, specifically an M1 to M2, pro- to anti-inflammatory transition, can be induced by biologic scaffold materials composed of extracellular matrix (ECM). The ECM-based immunomodulatory effect is thought to be mediated in part through recently identified matrix-bound nanovesicles (MBV) embedded within ECM. Isolated MBV was delivered via intravenous (i.v.) or peri-articular (p.a.) injection to rats with pristane-induced arthritis (PIA). The results of MBV administration were compared to intraperitoneal (i.p.) administration of methotrexate (MTX), the clinical standard of care. Relative to the diseased animals, i.p. MTX, i.v. MBV, and p.a. MBV reduced arthritis scores in both acute and chronic pristane-induced arthritis, decreased synovial inflammation, decreased adverse joint remodeling, and reduced the ratio of synovial and splenic M1 to M2 macrophages (p < 0.05). Both p.a. and i.v. MBV reduced the serum concentration of RA and PIA biomarkers CXCL10 and MCP-3 in the acute and chronic phases of disease (p < 0.05). Flow-cytometry revealed the presence of a systemic CD43hi/His48lo/CD206+, immunoregulatory monocyte population unique to p.a. and i.v. MBV treatment associated with disease resolution. The results show that the therapeutic efficacy of MBV is equal to that of MTX for the management of acute and chronic pristane-induced arthritis and, further, this effect is associated with modulation of local synovial macrophages and systemic myeloid populations.

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“…This highlights that the interplay between cells and ECM can be further modulated by the ECM's MBVs. [47][48][49]…”

Section: Molecular Mechanisms On Ecm Dynamics In the Ischemic Heartmentioning

confidence: 99%

Bidirectional Relationship Between Cardiac Extracellular Matrix and Cardiac Cells in Ischemic Heart Disease

et al. 2021

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Ischemic heart diseases (IHDs), including myocardial infarction and cardiomyopathies, are a leading cause of mortality and morbidity worldwide. Cardiac-derived stem and progenitor cells have shown promise as a therapeutic for IHD but are limited by poor cell survival, limited retention, and rapid washout. One mechanism to address this is to encapsulate the cells in a matrix or three-dimensional construct, so as to provide structural support and better mimic the cells' physiological microenvironment during administration. More specifically, the extracellular matrix (ECM), the native cellular support network, has been a strong candidate for this purpose. Moreover, there is a strong consensus that the ECM and its residing cells, including cardiac stem cells, have a constant interplay in response to tissue development, aging, disease progression, and repair. When externally stimulated, the cells and ECM work together to mutually maintain the local homeostasis by initially altering the ECM composition and stiffness, which in turn alters the cellular response and behavior. Given this constant interplay, understanding the mechanism of bidirectional cell-ECM interaction is essential to develop better cell implantation matrices to enhance cell engraftment and cardiac tissue repair. This review summarizes current understanding in the field, elucidating the signaling mechanisms between cardiac ECM and residing cells in response to IHD onset. Furthermore, this review highlights recent advances in native ECM-mimicking cardiac matrices as a platform for modulating cardiac cell behavior and inducing cardiac repair.

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Matrix-Bound Nanovesicles: The Effects of Isolation Method upon Yield, Purity, and Function

Cited by 19 publications

References 84 publications

The Functional Role of Extracellular Matrix Proteins in Cancer

The Functional Role of Extracellular Matrix Proteins in Cancer

Immunomodulatory matrix-bound nanovesicles mitigate acute and chronic pristane-induced rheumatoid arthritis

Bidirectional Relationship Between Cardiac Extracellular Matrix and Cardiac Cells in Ischemic Heart Disease

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