Search

Processes that activate the immune system during lung transplantation can lead to primary graft dysfunction (PGD) or allograft rejection.We analyzed cytokine expression profiles after reperfusion and allograft outcomes in a cohort of patients (n=59) who underwent lung transplantation off-pump (n=26), with cardiopulmonary bypass (CPB; n=18), or with extracorporeal membrane oxygenation (ECMO; n=15). Peripheral blood was collected from patients at baseline and at 6 and 72 hours after reperfusion. To adjust for clinical differences between groups, we utilized a linear mixed model with overlap weighting.PGD3 was present at 48 or 72 hours after reperfusion in 7.7% (2/26) of off-pump cases, 20.0% (3/15) of ECMO cases, and 38.9% (7/18) of CPB cases (p=0.04). The ECMO and CPB groups had greater reperfusion-induced increases in MIP-1B, IL-6, IL-8, IL-9, IL1-ra, TNF-alpha, RANTES, eotaxin, IP-10, and MCP-1 levels than did the off-pump group. Cytokine expression profiles after reperfusion were not significantly different between ECMO and CPB groups.Our data suggest that, compared with an off-pump approach, the intraoperative use of ECMO or CPB during lung transplantation is associated with greater reperfusion-induced cytokine release and graft injury.

The need to develop wearable devices for personal health monitoring, diagnostics, and therapy has inspired the production of innovative on-demand, customizable technologies. Several of these technologies enable printing of raw electronic materials directly onto biological organs and tissues. However, few of them have been thoroughly investigated for biocompatibility of the raw materials on the cellular, tissue, and organ levels or with different cell types. In addition, highly accurate multiday in vivo monitoring using such on-demand, in situ fabricated devices has yet to be done. Presented herein is the first fully biocompatible, on-skin fabricated electronics for multiple cell types and tissues that can capture electrophysiological signals with high fidelity. While also demonstrating improved mechanical and electrical properties, the drawn-on-skin ink retains its properties under various writing conditions, which minimizes the variation in electrical performance. Furthermore, the drawn-on-skin ink shows excellent biocompatibility with cardiomyocytes, neurons, mice skin tissue, and human skin. The high signal-to-noise ratios of the electrophysiological signals recorded with the DoS sensor over multiple days demonstrate its potential for personalized, long-term, and accurate electrophysiological health monitoring.

Cell therapy trials for heart failure (HF) have shown modest improvement; however, the mechanisms underlying improvement in some patients but not others are not well understood. Although immune cells are important in the course of HF, our understanding of the immune processes in HF is limited. The objective of this study was to evaluate associations between temporal changes in peripheral blood (PB) cell subpopulations and improved outcome in patients with chronic ischemic cardiomyopathy after bone marrow-derived mononuclear cell therapy or placebo in the FOCUS-CCTRN trial. Peripheral blood was collected at days 0, 1, 30, 90, and 180 from consented participants. We used flow cytometry to compare PB populations in patients with the best (cohort 1) or worst functional outcome (cohort 2) in three primary endpoints: left ventricular (LV) ejection fraction, LV end-systolic volume, and maximal oxygen consumption (VO2 max). A linear mixed model was used to assess changes over time in 32 cell populations. The difference between each time point and baseline was calculated as linear contrast. Compared with cohort 2, patients who improved (cohort 1) had a higher frequency of CD45+CD19+ B cells at days 0, 1, 90, and 180. CD11B+ cells increased over baseline at day 1 in both cohorts and remained higher in cohort 2 until day 30. CD45+CD133+ progenitor cells decreased over baseline at day 30 in cohort 1. We identified specific cell subpopulations associated with improved cardiac function in patients with chronic LV dysfunction. These findings may improve patient selection and prediction of outcomes in cell therapy trials.

To expand the application of perfusion decellularization beyond isolated single organs, we used the native vasculature of adult and neonatal rats to systemically decellularize the organs of a whole animal in situ. Acellular scaffolds were generated from kidney, liver, lower limb, heart‐lung system, and a whole animal body, demonstrating that perfusion decellularization technology is applicable to any perfusable tissue, independent of age. Biochemical and histological analyses demonstrated that organs and organ systems (heart‐lung pair and lower limb) were successfully decellularized, retaining their extracellular matrix (ECM) structure and organ‐specific composition, as evidenced by differences in organ‐specific scaffold stiffness. Altogether, we demonstrated that organs, organ systems and whole animal bodies can be perfusion decellularized while retaining ECM components and biomechanics., Representative images from systemic perfusion decellularization of an adult female whole rat body. Histological staining of excised organs and organs systems shows the absence of cells yet maintenance of tissue‐specific characteristics.

Background Primary graft dysfunction (PGD) is the most important determinant of morbidity and mortality after lung transplantation, but its definition has evolved over the past decade. The implications of this refinement in clinical definition have not been evaluated. In this single-center study, we compared PGD incidence, risk factors, and outcomes using the 2005 and the updated-2016 International Society of Heart and Lung Transplantation guidelines for PGD grading in lung transplant patients. Methods In this retrospective study, we extracted data from the medical records of 127 patients who underwent lung transplantation between 1/1/2016-12/31/2018. PGD was defined as PGD3 present at 48 and/or 72 hours post-reperfusion. We used the 2005 and the updated 2016 guidelines to assess clinical risk factors, outcomes, and baseline biomarkers for PGD. Results On the basis of the 2016 and 2005 guidelines, we identified PGD in 37% and 26% of patients, respectively. PGD was significantly associated with extracorporeal life support, large body mass index, and restrictive lung disease using the 2016 but not the 2005 guidelines. Based on the 2016 guidelines, pretransplant levels of several biomarkers were associated with PGD; using the 2005 guidelines, only increased interleukin-2 levels were significantly associated with PGD. No preoperative biomarkers were associated with PGD using either guidelines after adjusting for clinical variables. Postoperative morbidity and 1-year mortality were similar regardless of guidelines used. Conclusions Our findings suggest that refinements in the PGD scoring system have improved the detection of graft injury and associated risk factors without changing its ability to predict postoperative morbidity and mortality.

Exogenous cell-based therapy has emerged as a promising new strategy to facilitate repair of hearts damaged by acute or chronic injury. However, the field of cell-based therapy is handicapped by the lack of standardized definitions and terminology, making comparisons across studies challenging. Even the term ‘stem cell therapy’ is misleading because only a small percentage of cells derived from adult bone marrow, peripheral blood, or adipose tissue meets the accepted haematopoietic or developmental definition of stem cells. Furthermore, cells (stem or otherwise) are dynamic biological products, meaning that their surface-marker expression, phenotypic and functional characteristics, and the products they secrete in response to their microenvironment can change. It is also important to point out that most surface markers are seldom specific for a cell type. In this article, we discuss the lack of consistency in the descriptive terminology used in cell-based therapies and offer guidelines aimed at standardizing nomenclature and definitions to improve communication among investigators and the general public.