Characterization of a Vimentinhigh /Nestinhigh proteome and tissue regenerative secretome generated by human pancreas-derived mesenchymal stromal cells.

Multipotent/mesenchymal stromal cells (MSCs) exist within a variety of postnatal tissues; however, global proteomic analyses comparing tissue-specific MSC are limited. Using human bone marrow (BM)-derived MSCs as a gold standard, we used label-free mass spectrometry and functional assays to characterize the proteome, secretome, and corresponding function of human pancreas-derived MSCs (Panc-MSCs) with a classical phenotype (CD90+/CD73+/CD105+/CD45-/CD31-). Both MSC subtypes expressed mesenchymal markers vimentin, α-SMA, and STRO-1; however, expression of nestin was increased in Panc-MSCs. Accordingly, these Vimentinhigh /Nestinhigh cells were isolated from fresh human pancreatic islet and non-islet tissues. Next, we identified expression of >60 CD markers shared between Panc-MSCs and BM-MSCs, including validated expression of CD14. An additional 19 CD markers were differentially expressed, including reduced pericyte-marker CD146 expression on Panc-MSCs. Panc-MSCs also showed reduced expression of proteins involved in lipid and retinoid metabolism. Accordingly, Panc-MSCs showed restricted responses to adipogenic stimuli in vitro, although both MSC types demonstrated trilineage differentiation. In contrast, Panc-MSCs demonstrated accelerated growth kinetics and competency to pro-neurogenic stimuli in vitro. The secretome of Panc-MSCs was highly enriched for proteins associated with vascular development, wound healing and chemotaxis. Similar to BM-MSCs, Panc-MSCs conditioned media augmented endothelial cell survival, proliferation, and tubule formation in vitro. Importantly, the secretome of both MSC types was capable of stimulating chemotactic infiltration of murine endothelial cells in vivo and reduced hyperglycemia in STZ-treated mice following intrapancreatic injection. Overall, this study provides foundational knowledge to develop Panc-MSCs as a unique MSC subtype with functional properties beneficial in regenerative medicine for diabetes and vascular disease.

Predictors of triage pain assessment and subsequent pain management among pediatric patients presenting to the emergency department.

BACKGROUND: Pediatric patients with pain of various causes present to the emergency department. Appropriate assessment and management of pain are important aspects of emergency department treatment. However, only a few studies have identified the predictors of both outcomes. This study aimed to evaluate the rate of pain assessment at triage and subsequent management and to identify the predictors of each outcome. METHODS: This was a multi-center retrospective study based at five community emergency departments. Pediatric patients (< 18 years) with pain or injury who presented to the emergency department between February 2018 and May 2018 were included. In addition to patient demographics, the initial pain assessment at triage, reason for visit, and time to analgesia were determined. Further, the type and route of analgesia were identified in patients who received analgesia. Univariate and multivariable regression models were used to identify predictors of pain assessment and management. RESULTS: There were 4,128 patients with an average age of 9.6 years, and 49.1% of them were female. Only 74.2% of the patients underwent assessment for pain at triage, and 18.3% received analgesia. The median time to analgesia was 95 (IQR: 49-154) min. Most patients presented with head/neck (36.1%), upper limb (21.6%), and lower limb (19.9%) pain. The oral route was the most common analgesia delivery method (67.4%), and ibuprofen and acetaminophen were the primary agents used. Younger age, higher acuity, and presenting with head or neck pain were independent predictors of pain assessment at triage, while children 3-5 years and those with lower extremity pain were more likely to receive analgesia. CONCLUSION: Although pain assessment at triage has improved in pediatric patients, there is still a major deficiency in adequate pain management. Our study highlights predictors of pain assessment and management that can be considered for improved pediatric care.