Dataset Information

Role of extracellular matrix in the biomechanical behavior of pancreatic tissue.

ABSTRACT: Correlating the biomechanical properties of tissue with its function is an emerging area of research with potential impact in diagnostics, therapeutics, and prognostics. A critical stepping-stone in developing structure-function models is creating methods that can correlate the tissue structure with its mechanical behavior. As an initial step in addressing this challenge, we have characterized the mechanical behavior of unprocessed pancreatic tissue using optical fiber polarimetric elastography. To correlate the observed behavior to physiologically relevant structural features, a series of architectures are designed and fabricated using 3D printing. The mechanical response of the 3D printed elastomeric structures is analyzed using compressive testing and modeled using finite element analysis. The biomechanical behavior and buckling point of the 3D printed structures is used to create a calibration curve to understand the measured response of the resected pancreatic tissue. Based on the modeling and biomimetic results, the biomechanical behavior of pancreatic tissue is likely due to the collagen IV network.

SUBMITTER: Hudnut AW

PROVIDER: S-EPMC6905626 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of extracellular matrix in the biomechanical behavior of pancreatic tissue.

Hudnut Alexa W AW Lash-Rosenberg Lian L Xin An A Doblado Juan A Leal JAL Zurita-Lopez Cecilia C Wang Qiming Q Armani Andrea M AM

ACS biomaterials science & engineering 20180327 5

Correlating the biomechanical properties of tissue with its function is an emerging area of research with potential impact in diagnostics, therapeutics, and prognostics. A critical stepping-stone in developing structure-function models is creating methods that can correlate the tissue structure with its mechanical behavior. As an initial step in addressing this challenge, we have characterized the mechanical behavior of unprocessed pancreatic tissue using optical fiber polarimetric elastography. ...[more]

PMID: 31828218

Similar Datasets

Project description:Decellularized-organ-derived extracellular matrix (dECM) has been used for many years in tissue engineering and regenerative medicine. The manufacturing of hydrogels from dECM allows to make use of the pro-regenerative properties of the ECM and, simultaneously, to shape the material in any necessary way. The objective of the present project was to investigate differences between cardiovascular tissues (left ventricle, mitral valve, and aorta) with respect to generating dECM hydrogels and their interaction with cells in 2D and 3D. The left ventricle, mitral valve, and aorta of porcine hearts were decellularized using a series of detergent treatments (SDS, Triton-X 100 and deoxycholate). Mass spectrometry-based proteomics yielded the ECM proteins composition of the dECM. The dECM was digested with pepsin and resuspended in PBS (pH 7.4). Upon warming to 37°C, the suspension turns into a gel. Hydrogel stiffness was determined for samples with a dECM concentration of 20 mg/mL. Adipose tissue-derived stromal cells (ASC) and a combination of ASC with human pulmonary microvascular endothelial cells (HPMVEC) were cultured, respectively, on and in hydrogels to analyze cellular plasticity in 2D and vascular network formation in 3D. Differentiation of ASC was induced with 10 ng/mL of TGF-β1 and SM22α used as differentiation marker. 3D vascular network formation was evaluated with confocal microscopy after immunofluorescent staining of PECAM-1. In dECM, the most abundant protein was collagen VI for the left ventricle and mitral valve and elastin for the aorta. The stiffness of the hydrogel derived from the aorta (6,998 ± 895 Pa) was significantly higher than those derived from the left ventricle (3,384 ± 698 Pa) and the mitral valve (3,233 ± 323 Pa) (One-way ANOVA, p = 0.0008). Aorta-derived dECM hydrogel drove non-induced (without TGF-β1) differentiation, while hydrogels derived from the left ventricle and mitral valve inhibited TGF-β1-induced differentiation. All hydrogels supported vascular network formation within 7 days of culture, but ventricular dECM hydrogel demonstrated more robust vascular networks, with thicker and longer vascular structures. All the three main cardiovascular tissues, myocardium, valves, and large arteries, could be used to fabricate hydrogels from dECM, and these showed an origin-dependent influence on ASC differentiation and vascular network formation.

Project description:Desmoplasia is a characteristic feature and a suspected mechanism of tumor progression in pancreatic ductal adenocarcinoma (PDAC). Main constituents of the stroma involve cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM). The aim of this study was to dissect the interaction of CAFs, ECM, and PDAC cells in both an in vitro setting and a large-scale clinical cohort study.Patients operated for PDAC were identified from our prospectively maintained clinical database. A standard pathology protocol was applied for pancreatoduodenectomy specimens also assessing CAF activation as either CAF grade 0 or CAF grade +. Interaction between a spectrum of pancreatic cancer cell lines (PCCs) and mouse embryonic fibroblasts (NIH 3T3) was assessed in a conditioned medium experimental setup.One hundred eleven patients operated for PDAC from 2001 to 2011 were identified. Univariate analysis disclosed CAF grade + (P = .030), positive M status (P < .001), and lymph node ratio (LNR) > 0.1 (P = .045) to impair overall survival. Independent prognostic factors were CAF grade (P = .050) and positive M status (P = .002). CAF grade correlated with N status (CC = 0.206, P = .030), LNR (CC = 0.187, P = .049), tumor size (CC = -0.275, P = .003), and M status (CC = 0.190, P = .045). In the in vitro setting, paracrine effects of pancreatic cancer cell resulted in morphological activation of fibroblasts and tumor cell differentiation-dependent increase of fibroblast growth. Paracrine effects of poorly differentiated PCCs led to an upregulation of Vimentin in NIH 3T3 fibroblasts. Paracrine effects of fibroblasts on their part promoted cancer cell motility in all PCCs. As the second stromal component, fibroblast-derived ECM resulted in significantly decreased proliferation depending on density and led to upregulation of ZEB1 in poorly differentiated PCCs.In PDAC patients, positive CAF grading was identified as a negative prognostic parameter correlating with positive N status, high LNR, positive M status, and smaller tumor size. Whereas bilateral interaction of PCCs and CAFs promotes tumor progression, ECM poses PCC growth restrictions. In summary, our study discloses differential effects of stromal components and may help to interpret heterogeneous results of former studies.

Dataset Information

Role of extracellular matrix in the biomechanical behavior of pancreatic tissue.

Publications

Role of extracellular matrix in the biomechanical behavior of pancreatic tissue.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets