Hypertension, but not body mass index, is predictive of increased pancreatic lipid content and islet dysfunction.

Pancreatic steatosis is thought to be a negative risk factor for pancreas transplant outcomes. Despite considering donor body mass index (BMI) and the visualization of intercalated fat as indicators of donor pancreas lipid content, transplant surgeons do not use a quantitative method to directly measure steatosis when deciding to transplant a pancreas. In this study, we used nondiabetic human pancreata donated for research to measure the pancreatic and islet-specific lipid content to determine which clinical markers correlate best with lipid content. Interestingly, we found that BMI and age correlate with increased pancreatic lipid content (Panc-LC) in men, but not women. Our findings further suggest that total Panc-LC correlates with an increase in islet lipid content for both men and women. We noted that pancreata donated from individuals with a history of hypertension have increased Panc-LC independent of donor BMI or sex. Moreover, we identify hypertension as a risk factor for reduced islet function after islet isolation. Together, our findings emphasize differences in pancreas graft quality related to pancreatic and islet lipid content, which may not be predicted by assessing BMI alone but may be influenced by a donor history of hypertension.

A human pancreatic ECM hydrogel optimized for 3-D modeling of the islet microenvironment.

Extracellular matrix (ECM) plays a multitude of roles, including supporting cells through structural and biochemical interactions. ECM is damaged in the process of isolating human islets for clinical transplantation and basic research. A platform in which islets can be cultured in contact with natural pancreatic ECM is desirable to better understand and support islet health, and to recapitulate the native islet environment. Our study demonstrates the derivation of a practical and durable hydrogel from decellularized human pancreas that supports human islet survival and function. Islets embedded in this hydrogel show increased glucose- and KCl-stimulated insulin secretion, and improved mitochondrial function compared to islets cultured without pancreatic matrix. In extended culture, hydrogel co-culture significantly reduced levels of apoptosis compared to suspension culture and preserved controlled glucose-responsive function. Isolated islets displayed altered endocrine and non-endocrine cell arrangement compared to in situ islets; hydrogel preserved an islet architecture more similar to that observed in situ. RNA sequencing confirmed that gene expression differences between islets cultured in suspension and hydrogel largely fell within gene ontology terms related to extracellular signaling and adhesion. Natural pancreatic ECM improves the survival and physiology of isolated human islets.

Proteome-wide and matrisome-specific alterations during human pancreas development and maturation.

The extracellular matrix (ECM) is unique to each tissue and capable of guiding cell differentiation, migration, morphology, and function. The ECM proteome of different developmental stages has not been systematically studied in the human pancreas. In this study, we apply mass spectrometry-based quantitative proteomics strategies using N,N-dimethyl leucine isobaric tags to delineate proteome-wide and ECM-specific alterations in four age groups: fetal (18-20 weeks gestation), juvenile (5-16 years old), young adults (21-29 years old) and older adults (50-61 years old). We identify 3,523 proteins including 185 ECM proteins and quantify 117 of them. We detect previously unknown proteome and matrisome features during pancreas development and maturation. We also visualize specific ECM proteins of interest using immunofluorescent staining and investigate changes in ECM localization within islet or acinar compartments. This comprehensive proteomics analysis contributes to an improved understanding of the critical roles that ECM plays throughout human pancreas development and maturation.

Use of face coverings in public during the COVID-19 pandemic: an observational study.

Public health agencies have recommended that the public wear face coverings, including face masks, to mitigate COVID-19 transmission. However, the extent to which the public has adopted this recommendation is unknown. An observational study of 3,271 members of the public in May and June 2020 examined face covering use at grocery stores across Wisconsin. We found that only 41.2% used face coverings. Individuals who appeared to be female or older adults had higher odds of using face coverings. Additionally, location-specific variables such as expensiveness of store, county-level population and county-level COVID-19 case prevalence were associated with increased odds of using face coverings. To our knowledge, this is the first direct observational study examining face covering behavior by the public in the U.S., and our findings have implications for public health agencies during the COVID-19 pandemic.

Extracellular matrix scaffold and hydrogel derived from decellularized and delipidized human pancreas.

Extracellular matrix (ECM) plays an important developmental role by regulating cell behaviour through structural and biochemical stimulation. Tissue-specific ECM, attained through decellularization, has been proposed in several strategies for tissue and organ replacement. Decellularization of animal pancreata has been reported, but the same methods applied to human pancreas are less effective due to higher lipid content. Moreover, ECM-derived hydrogels can be obtained from many decellularized tissues, but methods have not been reported to obtain human pancreas-derived hydrogel. Using novel decellularization methods with human pancreas we produced an acellular, 3D biological scaffold (hP-ECM) and hydrogel (hP-HG) amenable to tissue culture, transplantation and proteomic applications. The inclusion of a homogenization step in the decellularization protocol significantly improved lipid removal and gelation capability of the resulting ECM, which was capable of gelation at 37 °C in vitro and in vivo, and is cytocompatible with a variety of cell types and islet-like tissues in vitro. Overall, this study demonstrates the characterisation of a novel protocol for the decellularization and delipidization of human pancreatic tissue for the production of acellular ECM and ECM hydrogel suitable for cell culture and transplantation applications. We also report a list of 120 proteins present within the human pancreatic matrisome.