Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model.

In pancreatic ductal adenocarcinoma (PDAC), the abundant stromal cells which comprise the tumor microenvironment constitute more than 90% of the primary tumor bulk. Moreover, this desmoplastic environment has been found to be three times stiffer than normal pancreas tissue. Despite the importance of studying the desmoplastic environment of PDAC, there is still a lack of models designed to adequately recapitulate this complex stiff microenvironment, a critical hallmark of the disease that has been shown to induce chemoresistance.

Tracheal squamous metaplasia in children with endotracheal intubation or tracheostomy.

Objectives: In the present study, tracheal epithelial biopsy samples between intubated children, children with tracheostomy and a control group of non-intubated children are compared with respect to their degree of normal differentiation versus the presence of squamous metaplasia.

Methods: Tracheal epithelial biopsies were obtained from intubated neonates undergoing tracheostomy, children with tracheostomy undergoing suprastomal granuloma excision and non-intubated control children undergoing laryngoscopy and bronchoscopy. Paraffin tissue blocks were sectioned at 5 μm thickness and subjected to both routine Hematoxylin and Eosin (H&E) staining and immunostained with the relevant antibodies for markers of epithelial differentiation including B-tubulin, CC10, Muc5ac, P63, keratin5 and keratin14.

Differential epithelial growth in tissue-engineered larynx and trachea generated from postnatal and fetal progenitor cells.

Postnatal organ-specific stem and progenitor cells are an attractive potential donor cell for tissue-engineering because they can be harvested autologous from the recipient and have sufficient potential to regenerate the tissue of interest with less risk for ectopic growth or tumor formation compared to donor cells from embryonic or fetal sources. We describe the generation of tissue-engineered larynx and trachea (TELT) from human and mouse postnatal organoid units (OU) as well as from human fetal OU. Mouse TELT contained differentiated respiratory epithelium lining large lumens, cartilage and smooth muscle.

Establishing Proximal and Distal Regional Identities in Murine and Human Tissue-Engineered Lung and Trachea.

The cellular and molecular mechanisms that underpin regeneration of the human lung are unknown, and the study of lung repair has been impeded by the necessity for reductionist models that may exclude key components. We hypothesized that multicellular epithelial and mesenchymal cell clusters or lung organoid units (LuOU) could be transplanted to recapitulate proximal and distal cellular structures of the native lung and airways. Transplantation of LuOU resulted in the growth of tissue-engineered lung (TELu) that contained the necessary cell types consistent with native adult lung tissue and demonstrated proliferative cells at 2 and 4 weeks.