Functional human heart tissues, derived from human induced pluripotent stem (iPS) cells and cultivated in mouse heart scaffolds, are reported in Nature Communications this week. This novel strategy for engineering personalized heart constructs could help study early heart formation or, eventually, find application in preclinical testing.
Engineering heart tissues through a process of re-seeding heart muscles into decellularized whole hearts has shown promise in a rat model; however, previous attempts to repopulate decellularized mouse hearts with human embryonic stem cells have failed to generate functional heart constructs.
Lei Yang and colleagues engineered human heart tissues by repopulating whole decellularized mouse hearts with multipotential cardiovascular progenitors - the earliest cells in human heart development - derived from human iPS cells. These cells successfully grew and developed in into heart muscles and, after 20 days of blood supply, the authors report that approximately 90% of constructs created displayed spontaneous contractions. They also exhibited expected electrophysiological characteristics and responded normally to drugs that are known to stimulate heartbeat. The authors suggest that this finding indicates potential preclinical applications for these engineered heart tissues.
They note, however, that the mechanical force generated by the tissues is currently insufficient for pumping blood and electrical conduction is slow; therefore, further study is needed in order to improve the functionality of these constructs.