The Renewal and Differentiation of Isl1 + Cardiovascular Progenitors Are Controlled by a Wnt/β-Catenin Pathway

Isl1 + cardiovascular progenitors and their downstream progeny play a pivotal role in cardiogenesis and lineage diversification of the heart. The mechanisms that control their renewal and differentiation are largely unknown. Herein, we show that the Wnt/β-catenin pathway is a major component by which cardiac mesenchymal cells modulate the prespecification, renewal, and differentiation of isl1 + cardiovascular progenitors. This microenvironment can be reconstituted by a Wnt3a-secreting feeder layer with ES cell-derived, embryonic, and postnatal isl1 + cardiovascular progenitors. In vivo activation of β-catenin signaling in isl1 + progenitors of the secondary heart field leads to their massive accumulation, inhibition of differentiation, and outflow tract (OFT) morphogenic defects. In addition, the mitosis rate in OFT myocytes is significantly reduced following β-catenin deletion in isl1 + precursors. Agents that manipulate Wnt signals can markedly expand isl1 + progenitors from human neonatal hearts, a key advance toward the cloning of human isl1 + heart progenitors. © 2007 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Trends and Outcomes of Cardiac Transplantation in the Lowest Urgency Candidates

Background Because of discrepancies between donor supply and recipient demand, the cardiac transplantation process aims to prioritize the most medically urgent patients. It remains unknown how recipients with the lowest medical urgency compare to others in the allocation process. We aimed to examine differences in clinical characteristics, organ allocation patterns, and outcomes between cardiac transplantation candidates with the lowest and highest medical urgency. Methods and Results We performed a retrospective analysis of the United Network for Organ Sharing database. Patients listed for cardiac transplantation between January 2011 and May 2020 were stratified according to status at time of transplantation. Baseline recipient and donor characteristics, waitlist survival, and posttransplantation outcomes were compared in the years before and after the 2018 allocation system change. Lower urgency patients in the old system were older (58.5 versus 56 years) and more likely female (54.4% versus 23.8%) compared with the highest urgency patients, and these trends persisted in the new system (P<0.001, all). Donors for the lowest urgency patients were more likely older, female, or have a history of cytomegalovirus, hepatitis C, or diabetes (P<0.01, all). The lowest urgency patients had longer waitlist times and under the new allocation system received organs from shorter distances with decreased ischemic times (178 miles versus 269 miles, 3.1 versus 3.5 hours; P<0.001, all). There was no difference in posttransplantation survival (P<0.01, all). Conclusions Patients transplanted as lower urgency receive hearts from donors with additional comorbidities compared with higher urgency patients, but outcomes are similar at 1 year