Development of a Decellularized Porcine Esophageal Matrix for Potential Applications in Cancer Modeling

Abstract

Many decellularized extracellular matrix-derived whole organs have been widely used in studies of tissue engineering and cancer models. However, decellularizing porcine esophagus to obtain decellularized esophageal matrix (DEM) for potential biomedical applications has not been widely investigated. In this study a modified decellularization protocol was employed to prepare a porcine esophageal DEM for the study of cancer cell growth. The cellular removal and retention of matrix components in the porcine DEM were fully characterized. The microstructure of the DEM was observed using scanning electronic microscopy. Human esophageal squamous cell carcinoma (ESCC) and human primary esophageal fibroblast cells (FBCs) were seeded in the DEM to observe their growth. Results show that the decellularization process did not cause significant loss of mechanical properties and that blood ducts and lymphatic vessels in the submucosa layer were also preserved. ESCC and FBCs grew on the DEM well and the matrix did not show any toxicity to cells. When FBS and ESCC were cocultured on the matrix, they secreted more periostin, a protein that supports cell adhesion on matrix. This study shows that the modified decellularization protocol can effectively remove the cell materials and maintain the microstructure of the porcine esophageal matrix, which has the potential application of studying cell growth and migration for esophageal cancer models.

Viscoelastic Properties of Acellular Matrices of Porcine Esophageal Mucosa and Comparison with Acellular Matrices of Porcine Small Intestine Submucosa and Bovine Pericardium

“…In the study published by Chaitin et al [ 47 ], they demonstrate that the decellularization process preserves the mechanical integrity and extracellular matrix composition of esophageal tissue. In that study, it was observed that native esophageal mucosa exhibited a maximum extension stress between 1.5 and 2.0 MPa at around 450% extension, while the decellularized tissue showed a maximum extension stress between 4.0 MPa and 4.5 MPa at 600% extension.…”

Periostin: a predictable molecule to prognosis and chemotherapy responses of gastrointestinal and hepato-biliary-pancreatic malignant tumors?

“…In early experiments, gene detection at the mRNA and protein levels confirmed POSTN overexpression in esophageal squamous cell carcinoma (ESCC), which may be related to the communication between cells and ECM [27]. Subsequent studies in organotypic (three-dimensional) cell models and microarray experiments further confirmed its strong association with tumor cell migration and invasion in esophageal squamous cell carcinoma [28,29]. Another clinical trial also demonstrated that the upregulated rate of POSTN had a significant correlation with lymph node 6 metastasis, adventitia invasion, and TNM stage [30].…”

Osteomatrix as a personalized 3D tissue-specific invasion test-bed for oral carcinoma

“…9,62 Decellularized extracellular matrices used in the development of oral cancer models by previous studies were confined to studying the primary site of cancer with no information on metastatic invasion. [63][64][65]…”