Decellularized skeletal muscle as an in vitro model for studying drug-extracellular matrix interactions

Wassenaar, Jean W.; Boss, Gerry R.; Christman, Karen L.

doi:10.1016/j.biomaterials.2015.06.033

Cited by 31 publications

(19 citation statements)

References 27 publications

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“…This finding is consistent with previous studies that created dME based scaffolds for musculoskeletal tissue repair (e.g. bone, muscle, tendon), in which evidence of dME promoting recellularization and organic molecule adsorption had been reported [57][58][59]. We also confirmed that dMEP scaffolds contained a significantly higher initial collagen components than the PCL scaffolds, and that this component was accessible to exogenous proteases.…”

Section: Discussionsupporting

confidence: 92%

Development of A Decellularized Meniscus Matrix-Based Nanofibrous Scaffold for Meniscus Tissue Engineering

Xia

Kim

Bansal

et al. 2020

Preprint

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The meniscus plays a critical role in knee mechanical function but is commonly injured given its central load bearing role. In the adult, meniscus repair is limited, given the low number of endogenous cells, the density of the matrix, and the limited vascularity. Menisci are fibrocartilaginous tissues composed of a micro-/nano-fibrous extracellular matrix (ECM) and a mixture of chondrocyte-like and fibroblast-like cells. Here, we developed a fibrous scaffold system that consists of bioactive components (decellularized meniscus ECM (dME) within a poly(e-caprolactone) material) fashioned into a biomimetic morphology (via electrospinning) to support and enhance meniscus cell function and matrix production. This work supports that the incorporation of dME into synthetic nanofibers increased hydrophilicity of the scaffold, leading to enhanced meniscus cell spreading, proliferation, and fibrochondrogenic gene expression. This work identifies a new biomimetic scaffold for therapeutic strategies to substitute or replace injured meniscus tissue.STATEMENT OF SIGNIFICANCEIn this study, we show that a scaffold electrospun from a combination of synthetic materials and bovine decellularized meniscus ECM provides appropriate signals and a suitable template for meniscus fibrochondrocyte spreading, proliferation, and secretion of collagen and proteoglycans. Material characterization and in vitro cell studies support that this new bioactive material is susceptible to enzymatic digestion and supports meniscus-like tissue formation.

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Section: Discussionsupporting

confidence: 92%

Development of A Decellularized Meniscus Matrix-Based Nanofibrous Scaffold for Meniscus Tissue Engineering

Xia

Kim

Bansal

et al. 2020

Preprint

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“…Interestingly, it was shown that normalizing tumor ECM environment was able to “revert” cancer cell neoplastic phenotype [ 15 ] and limit tumor growth and dissemination [ 16 ], highlighting the essential role of ECM physicochemical properties on cancer development. These ECM-guided cell biological changes suggest potential therapeutic approaches that target ECM rather than cancer cells for treatment or that treatments can be ineffective if, for example, a dense ECM or binding with the ECM limits drug availability [ 10 , 17 , 18 ]. Therefore, it is important to study cancer cell biology and regulatory mechanisms in tissue-mimicking microenvironments, which are able to facilitate unveiling the nature of carcinogenic processes when it comes to cancer cell adhesion, proliferation, migration, invasion, metastasis, and drug treatment in native tissue space [ 19 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

Distinct phenotypes of cancer cells on tissue matrix gel

Ruud

Hiscox

et al. 2020

Breast Cancer Res

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Background: Breast cancer cells invading the connective tissues outside the mammary lobule or duct immerse in a reservoir of extracellular matrix (ECM) that is structurally and biochemically distinct from that of their site of origin. The ECM is a spatial network of matrix proteins, which not only provide physical support but also serve as bioactive ligands to the cells. It becomes evident that the dimensional, mechanical, structural, and biochemical properties of ECM are all essential mediators of many cellular functions. To better understand breast cancer development and cancer cell biology in native tissue environment, various tissue-mimicking culture models such as hydrogel have been developed. Collagen I (Col I) and Matrigel are the most common hydrogels used in cancer research and have opened opportunities for addressing biological questions beyond the two-dimensional (2D) cell cultures. Yet, it remains unclear whether these broadly used hydrogels can recapitulate the environmental properties of tissue ECM, and whether breast cancer cells grown on CoI I or Matrigel display similar phenotypes as they would on their native ECM. Methods: We investigated mammary epithelial cell phenotypes and metabolic profiles on animal breast ECMderived tissue matrix gel (TMG), Col I, and Matrigel. Atomic force microscopy (AFM), fluorescence microscopy, acini formation assay, differentiation experiments, spatial migration/invasion assays, proliferation assay, and nuclear magnetic resonance (NMR) spectroscopy were used to examine biological phenotypes and metabolic changes. Student's t test was applied for statistical analyses. Results: Our data showed that under a similar physiological stiffness, the three types of hydrogels exhibited distinct microstructures. Breast cancer cells grown on TMG displayed quite different morphologies, surface receptor expression, differentiation status, migration and invasion, and metabolic profiles compared to those cultured on Col I and Matrigel. Depleting lactate produced by glycolytic metabolism of cancer cells abolished the cell proliferation promoted by the non-tissue-specific hydrogel. Conclusion: The full ECM protein-based hydrogel system may serve as a biologically relevant model system to study tissue-and disease-specific pathological questions. This work provides insights into tissue matrix regulation of cancer cell biomarker expression and identification of novel therapeutic targets for the treatment of human cancers based on tissue-specific disease modeling.

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“…Because Matrigel is derived from a tumor of the basement membrane, and promotes cell growth, it is particularly beneficial in drug screening and development 108 , 109 , 110 . The production of 3D cell cultures using ECM scaffolds developed through decellularization has been, or is currently being, demonstrated in cardiac, adipose, hepatic, pleural, vascular, skeletal muscle, neuronal, and renal tissues 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 …”

Section: Future Directionsmentioning

confidence: 99%

3D tissue engineering, an emerging technique for pharmaceutical research

Jensen

Morrill

Huang

2018

Acta Pharmaceutica Sinica B

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Tissue engineering and the tissue engineering model have shown promise in improving methods of drug delivery, drug action, and drug discovery in pharmaceutical research for the attenuation of the central nervous system inflammatory response. Such inflammation contributes to the lack of regenerative ability of neural cells, as well as the temporary and permanent loss of function associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and traumatic brain injury. This review is focused specifically on the recent advances in the tissue engineering model made by altering scaffold biophysical and biochemical properties for use in the treatment of neurodegenerative diseases. A portion of this article will also be spent on the review of recent progress made in extracellular matrix decellularization as a new and innovative scaffold for disease treatment.

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Decellularized skeletal muscle as an in vitro model for studying drug-extracellular matrix interactions

Cited by 31 publications

References 27 publications

Development of A Decellularized Meniscus Matrix-Based Nanofibrous Scaffold for Meniscus Tissue Engineering

Development of A Decellularized Meniscus Matrix-Based Nanofibrous Scaffold for Meniscus Tissue Engineering

Distinct phenotypes of cancer cells on tissue matrix gel

3D tissue engineering, an emerging technique for pharmaceutical research

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