Surgical Approaches to Create Murine Models of Human Wound Healing

Wound repair is a complex biologic process which becomes abnormal in numerous disease states. Although in vitro models have been important in identifying critical repair pathways in specific cell populations, in vivo models are necessary to obtain a more comprehensive and pertinent understanding of human wound healing. The laboratory mouse has long been the most common animal research tool and numerous transgenic strains and models have been developed to help researchers study the molecular pathways involved in wound repair and regeneration. This paper aims to highlight common surgical mouse models of cutaneous disease and to provide investigators with a better understanding of the benefits and limitations of these models for translational applications

An Information Theoretic, Microfluidic-Based Single Cell Analysis Permits Identification of Subpopulations among Putatively Homogeneous Stem Cells

An incomplete understanding of the nature of heterogeneity within stem cell populations remains a major impediment to the development of clinically effective cell-based therapies. Transcriptional events within a single cell are inherently stochastic and can produce tremendous variability, even among genetically identical cells. It remains unclear how mammalian cellular systems overcome this intrinsic noisiness of gene expression to produce consequential variations in function, and what impact this has on the biologic and clinical relevance of highly ‘purified’ cell subgroups. To address these questions, we have developed a novel method combining microfluidic-based single cell analysis and information theory to characterize and predict transcriptional programs across hundreds of individual cells. Using this technique, we demonstrate that multiple subpopulations exist within a well-studied and putatively homogeneous stem cell population, murine long-term hematopoietic stem cells (LT-HSCs). These subgroups are defined by nonrandom patterns that are distinguishable from noise and are consistent with known functional properties of these cells. We anticipate that this analytic framework can also be applied to other cell types to elucidate the relationship between transcriptional and phenotypic variation

Evaluation of the Sex-and-Age-Specific Effects of PM2.5 on Hospital Readmission in the Presence of the Competing Risk of Mortality in the Medicare Population of Utah 1999–2009

Acute ambient air pollution exposure increases risk of cardiac events. We evaluated sex-and-age-specific effects of PM2.5 on hospital readmission and death among 19,602 Medicare beneficiaries (Nevents = 30,510) who survived cardiovascular events including myocardial infarction (MI), heart failure (HF), ischemic heart disease (IHD), and cardiac arrhythmias in Utah from 1999–2009. Fine and Gray regression jointly modeled the effect of PM2.5 on readmission hazard rates while allowing for the competing risk of death. Models were stratified by age and sex and adjusted for Charlson Comorbidity Index, dual enrollment in Medicare Parts A and B, temperature, and household income. There were 2032 cardiac readmissions and 1420 deaths after discharge. Among males age 65–74 years admitted for HF, a 10 μm/m3 increase in PM2.5 was associated with a 30% increase in risk of readmission (p = 0.01). Among females age 75–84 admitted for HF, PM2.5 was associated with a 22% increase in risk of readmission (p = 0.01). Among females age 75–84 years admitted for IHD, PM2.5 was associated with a 25% decrease in readmission (p = 0.01), however this was explained by a 36% increase in risk of death (p = 0.01). Exposure to PM2.5 was associated with increased risk of readmission and death. Associations were dependent upon age, sex, and index condition

Minimally Invasive versus Full Sternotomy SAVR in the Era of TAVR: An Institutional Review

In the era of advancing transcatheter aortic valve replacement (TAVR) technology, traditional open surgery remains a valuable intervention for patients who are not TAVR candidates. We sought to compare perioperative variables and postoperative outcomes of minimally invasive and full sternotomy surgical aortic valve replacement (SAVR) at a single institution. A retrospective analysis of 113 patients who underwent isolated SAVR via full sternotomy or upper hemi-sternotomy between January 2015 and December 2019 at the University of Utah Hospital was performed. Preoperative comorbidities and demographic information were not different among groups, with the exception of diabetes, which was significantly more common in the full sternotomy group (p = 0.01). Median procedure length was numerically shorter in the minimally invasive group but was not significant following the Bonferroni correction (p = 0.047). Other perioperative variables were not significantly different. The two groups showed no difference in the incidence of postoperative adverse events (p = 0.879). As such, minimally invasive SAVR via hemi-sternotomy remains a safe and effective alternative to full sternotomy for patients who meet the criteria for aortic valve replacement

Microfluidic single-cell transcriptional analysis rationally identifies novel surface marker profiles to enhance cell-based therapies.

Current progenitor cell therapies have only modest efficacy, which has limited their clinical adoption. This may be the result of a cellular heterogeneity that decreases the number of functional progenitors delivered to diseased tissue, and prevents correction of underlying pathologic cell population disruptions. Here, we develop a high-resolution method of identifying phenotypically distinct progenitor cell subpopulations via single-cell transcriptional analysis and advanced bioinformatics. When combined with high-throughput cell surface marker screening, this approach facilitates the rational selection of surface markers for prospective isolation of cell subpopulations with desired transcriptional profiles. We establish the usefulness of this platform in costly and highly morbid diabetic wounds by identifying a subpopulation of progenitor cells that is dysfunctional in the diabetic state, and normalizes diabetic wound healing rates following allogeneic application. We believe this work presents a logical framework for the development of targeted cell therapies that can be customized to any clinical application