Pediatric patients awaiting a heart transplant have high waitlist mortality. Several strategies have been utilized to decrease waiting times, but a mortality risk still exists. New medical technologies may improve waiting times and associated mortality. Ex situ heart perfusion (ESHP) is one such technology, which can decrease the impact of cold ischemia on the donor heart and allow for a longer out-of-body time. Adoption of such technology in pediatric heart transplantation will require support from end users, including patient and families. The aim of this qualitative study was to report the perspectives of families with experience related to pediatric HTx toward ESHP.Semistructured interviews were conducted with 12 parents or guardians of children who were awaiting or received heart transplantation. Interviews were transcribed, and data were analyzed using qualitative content analysis.Participants expressed varied awareness and knowledge of ESHP. Independent of their understanding of ESHP, all purported that ESHP was an excellent idea and that this technology should be implemented in the pediatric population. They did not identify fundamentally different ethical issues or concerns for ESHP being used relative to other medical technologies. Overall, most participants described consent processes for ESHP should be like any other procedure. All agreed that the surgeon should continue to describe the overall health of the donor heart, provide their medical recommendations, and allow families to have the final say.The concepts described by the parents and guardians are important in moving this novel technology forward. This information will serve the basis for knowledge translation that will provide educational resources to broaden the understanding and reach of ESHP.
Lung transplantation is the gold-standard treatment for end-stage lung disease, with over 4,600 lung transplantations performed worldwide annually. However, lung transplantation is limited by a shortage of available donor organs. As such, there is high waitlist mortality. Ex situ lung perfusion (ESLP) has increased donor lung utilization rates in some centers by 15%-20%. ESLP has been applied as a method to assess and recondition marginal donor lungs and has demonstrated acceptable short- and long-term outcomes following transplantation of extended criteria donor (ECD) lungs. Large animal (in vivo) transplantation models are required to validate ongoing in vitro research findings. Anatomic and physiologic differences between humans and pigs pose significant technical and anesthetic challenges. An easily reproducible transplant model would permit the in vivo validation of current ESLP strategies and the preclinical evaluation of various interventions designed to improve donor lung function. This protocol describes a porcine model of orthotopic left lung allotransplantation. This includes anesthetic and surgical techniques, a customized surgical checklist, troubleshooting, modifications, and the benefits and limitations of the approach.
Introduction Coronary artery disease (CAD), i.e. myocardial infarction and ischemic cardiomyopathy, is the global leading cause of death. Ischemia leads to loss of functional cardiomyocytes, which contributes to a variety of types of heart failure. Although conventional treatments including pharmacological therapy and coronary revascularization procedures exist, novel therapeutic approaches are still needed. The prospect of stem‐cell‐based therapies might have considerable therapeutic potential. Induced pluripotent stem cells (iPSCs) can be generated from a variety of somatic cells as a potential resource of replacement cells, making them ideal cellular models to provide a renewable source of cardiomyocytes for cell‐based therapy. However, an ideal cell type with superior cardiomyocyte (CM) potential has yet to be identified. Masseter muscle cells (MMC) characterized as Isl‐1 + cells, a genetic marker associated with stem and progenitor states, also contribute to various cardiovascular lineages and have similar embryological origins. We postulate the regenerative potential of masseter muscle cell lineages may yield valuable developmental and clinical insights in the identification of a cell source capable of enhanced cardiomyocyte differentiation and may be used in cell‐based therapy. This study aims to study the role of epigenetic memory in the cardiogenic potential of different lineages of iPSC. Methods A variety of cell sources including masseter muscle cells (MMC), dermal fibroblasts (Fib), bone marrow mesenchymal cells (BMC), and Trunk skeletal muscle cells (TMC) from mouse were isolated. These cell sources were then transfected with Yamanaka's factors (Oct4, Sox2, c‐Myc, and Klf‐4) to generate four lineages of iPSCs. These four iPSC cell lineages were differentiated into iPSC‐CMs via 3‐D culture protocols and analyzed for differences in their differentiation potential as well as the efficiency of differentiation. Cardiomyocytes differentiation was analyzed by spontaneous contractions, immunostaining, flow cytometry test, and patch clamp. The epigenetic signatures of somatic cells, iPSCs, and derived Cardiomyocytes were analyzed by Real‐time PCR. Methylation study was used to evaluate epigenetic memory of four lineages of iPSCs. Results Spontaneous beating was observed in 80% colonies of MMC‐derived iPSC‐cardiomyocytes (MMC‐CM), which was significantly higher than other groups. Cardiac genes Isl‐1, Nkx2.5, and GATA4 were also significantly upregulated in MMC‐CM. MMC‐CM exerted robust cardiac functional phenotype, indicated by enhanced contractility and electrophysiological properties. Low methylation levels of the cardiac mesodermal gene (Isl‐1) in MMC and M‐iPSC were similar to neonatal cardiomyocytes and were maintained in MMC‐CM. Cardiac genes were epigenetically silenced in other somatic cells. Conclusion iPSCs derived from masseter muscle cell sources have better cardiogenic differentiation capabilities than other somatic cell sources. Epigenetic memory significantly contributes to the prominent cardiogenic potential of masseter‐derived iPSCs. Support or Funding Information National Institutes of Health grants (HL110740)
Background: Adipose stem cells (ASC) from subcutaneous and visceral adipose tissues have been studied individually. However, it is unclear whether ASC from the two sources have different biological properties and, more importantly, whether one sub-type of ASC is more effective in treatment of CHF. This study was designed to address these concerns. Methods: Morphology, yield, proliferation, surface markers, and cytokine secretion of rat subcutaneous ASC (S-ASC) and visceral ASC (V-ASC) were analyzed. A rat model of myocardial infarction (MI) was established by occlusion of the LAD. 7 days after MI, S-ASC (n = 11), V-ASC (n = 11), and cell culture medium (Control, n = 7) were injected into the infarct rim, respectively. Cardiac function of the infarcted hearts was monitored with MRI for 6 months. Results: Both S-ASC and V-ASC exhibited a fibroblast-like morphology and expressed stromal cell markers (CD29, CD90 and CD105). No significant expression of hematopoietic markers (CD11b, CD34 and CD45) was found. Under appropriate conditions, both cells could differentiate to adipocyte- and osteocyte-like cells. Both of them expressed a significant level of HGF, IGF-1 and VEGF. As to their differences, V-ASC had approximately 3-times greater cell yield and a lower colony-formation rate (9.8±1.0% vs.13.5±2.6%) relative to S-ASC. In contrast, S-ASC showed a significantly greater growth rate (Doubling Time: 17.9 h vs. 26.0 h) relative to V-ASC. Both S-ASC and V-ASC-treated hearts showed a significantly greater left ventricular ejection fraction (LVEF, 58.3% and 56.7%) than the control group (LVEF, 47.2%) at end of 6 months. LVEF between the two ASC-treated groups was not significantly different. Finally, the implanted stem cells were readily detected in vivo with MRI for at least 6 months. Myocardial tissue sections showed existence of ASC and their locations matched with MRI signals. Conclusions: S-ASC and V-ASC share several biological characteristics. Both provide comparable significant improvement on cardiac function. Moreover, these implanted cells can be reliably tracked for at least 6 months using MRI. We conclude that the S-ASC and V-ASC are equally effective for treatment of heart failure.
Background Driveline infections (DLIs) are a common adverse event in patients on ventricular assist devices (VADs) with incidence ranging from 14% to 59%. DLIs have an impact on patients and the healthcare system with efforts to prevent DLIs being essential. Prior to our intervention, our program had no standard driveline management presurgery and postsurgery. The purpose of this Quality Improvement (QI) initiative was to reduce DLIs and related admissions among patients with VAD within the first year post implant. Methods In anticipation of the QI project, we undertook a review of the programs’ current driveline management procedures and completed a survey with patients with VAD to identify current barriers to proper driveline management. Retrospective data were collected for a pre-QI intervention baseline comparison group, which included adult patients implanted with a durable VAD between 1 January 2017 and 31 July 2018. A three-pronged care pathway (CP) was initiated among patients implanted during August 2018 to July 2019. The CP included standardised intraoperative, postoperative and predischarge teaching initiatives and tracking. Using statistical process control methods, DLIs and readmissions in the first year post implant were compared between patients in the CP group and non-CP patients. P-charts were used to detect special cause variation. Results A higher proportion of CP group patients developed a DLI in the first year after implant (52% vs 32%). None developed a DLI during the index admission, which differed from the non-CP group and met criteria for special cause variation. There was a downward trend in cumulative DLI-related readmissions among CP group patients (55% vs 67%). There was no association between CP compliance and development of DLIs within 1 year post implant. Conclusion The CP did not lead to a reduction in the incidence of DLIs but there was a decrease in the proportion of patients with DLIs during their index admission and those readmitted for DLIs within 1 year post implant. This suggests that the CP played a role in decreasing the impact of DLIs in this patient population. However, given the short time period of follow-up longer follow-up will be required to look for sustained effects.
