Anomalous origins of the coronary arteries: current knowledge and future perspectives.

PURPOSE OF REVIEW: The purpose of this review is to survey the contemporary literature surrounding congenital anomalies of origin of the coronary arteries and to identify remaining gaps in knowledge. RECENT FINDINGS: In recent years, lineage tracing analyses and mechanistic studies in model organisms have enhanced our understanding of the normal embryologic development of the coronary arteries, and how disruption of this intricate process can lead to congenital coronary anomalies. The true incidence of these anomalies remains unknown. Although a majority of cases are believed to be clinically silent, clinical presentation varies widely, from asymptomatic to sudden cardiac death. Cardiac computed tomography angiography and/or magnetic resonance angiography are the mainstay diagnostic modalities. Management of anomalous coronary arteries depends on the morphology and clinical presentation. Surgery is the gold-standard treatment for anomalous left coronary artery arising from the pulmonary artery and anomalous aortic origin of a coronary artery with intramural or interarterial course. SUMMARY: Several large multicenter initiatives are currently underway and should help address some of the numerous knowledge gaps surrounding the evaluation and management of anomalous coronary arteries.

Human liver sinusoidal endothelial cells support the development of functional human pluripotent stem cell-derived Kupffer cells.

In mice, the first liver-resident macrophages, known as Kupffer cells (KCs), are thought to derive from yolk sac (YS) hematopoietic progenitors that are specified prior to the emergence of the hematopoietic stem cell (HSC). To investigate human KC development, we recapitulated YS-like hematopoiesis from human pluripotent stem cells (hPSCs) and transplanted derivative macrophage progenitors into NSG mice previously humanized with hPSC-liver sinusoidal endothelial cells (LSECs). We demonstrate that hPSC-LSECs facilitate stable hPSC-YS-macrophage engraftment for at least 7 weeks. Single-cell RNA sequencing (scRNA-seq) of engrafted YS-macrophages revealed a homogeneous MARCO-expressing KC gene signature and low expression of monocyte-like macrophage genes. In contrast, human cord blood (CB)-derived macrophage progenitors generated grafts that contain multiple hematopoietic lineages in addition to KCs. Functional analyses showed that the engrafted KCs actively perform phagocytosis and erythrophagocytosis in vivo. Taken together, these findings demonstrate that it is possible to generate human KCs from hPSC-derived, YS-like progenitors.