The Beat Goes On: Human Heart Muscle From Pluripotent Stem Cells

Abstract

See related article, pages 47–59 In 2003, C. Zandonella reviewed in Nature how much was achieved of the 1999 promise to grow a functioning heart in the dish in a decade and what the perspectives were at that time.1 Today, more than a decade after its public prediction, the heart in the dish is still an unfulfilled dream, but repairing injured hearts with engineered myocardial tissue patches is a viable and increasingly realistic perspective in regenerative cardiology. This is not so much because of the progress in tissue engineering techniques but rather because of the dramatic advances in stem cell biology. In 1998, the first human embryonic stem cells (hESC) were described,2 and 3 years later the generation of cardiac myocytes from hESC.3 Despite widespread ethical concerns and strict legal restrictions in many countries of the world including the US and Germany, hESC proved to be enormously important for several reasons. First, they helped to better understand the earliest steps of human development and human stem cell biology, which differ in critical aspects from those in the mouse. Second, human ESC provided, for the first time, an unlimited cell source with an undisputed capacity to differentiate into essentially all types of cells of the body, including cardiac myocytes. Their discovery boosted cardiac tissue engineering principally by answering the question as to where the several hundred millions of human cardiac myocytes may come from that are necessary to make large myocardial patches.4 Third, ironically, the ethical concerns against hESC work stimulated and in some cases initiated the search for pluripotent alternatives that would be devoid of the regulatory and ethical problems of hESC. This motivation, combined with the technical experience acquired with mouse and human ESC cultures, was an important driver for the progress in stem cell …