Israeli scientists have conned human embryonic stem cells into generating beating human heart-muscle cells. The 10 co-authors of a paper in the August 2001 issue of The Journal of Clinical Investigation are cardiovascular, obstetrical and anatomy researchers at the Technion-Israel Institute of Technology (Haifa).
For starters, the team dispersed small clumps of three to 20 embryonic stem (ES) cells, seeded colonies of half a million cells into Petri dishes, then cultured them in suspension for seven to 10 days. During this incubation, the cells aggregated to form embryoid bodies (EB). They plated 1,884 of these EBs onto gelatin-coated dishes, and monitored them by electron microscopy for the emergence of cardiac-like contractions. As their paper noted, "Rhythmically contracting areas appeared at four to 22 days, in 153 (8.1%) of the 1,884 EBs studied. Their diameter ranged from 0.2 to 2 millimeters, and they continued to beat vigorously for up to five weeks (the longest period studied). The average spontaneous pulsation rate was 94 plus/ minus 33 beats per minute."
The team assessed the expression of several cardiac-specific genes in the human ES cell-derived muscle cells by PCR analysis. Myocytes from the contracting EBs expressed cardiac transcription factors and cardiac-specific genes, notably atrial and ventricular myosin light and heavy chains. In the normal human embryo, they noted, "heart formation begins with the initiation of differentiation by myocardial and endocardial precursors, and leads up to the formation of the cardiac valves." Adult cardiomyocytes, they said, "withdraw permanently from the cell cycle during differentiation; hence, any significant loss of cardiomyocytes (as occurs, for example, during myocardial infarction) is irreversible and leads to diminished cardiac function and progressive heart failure."
Their findings, the co-authors observe, suggest an "attractive application of these [embryonic] cells in cell replacement therapy." A novel potential approach for this situation, they propose, "may be the implantation of myogenic cells within the infarcted tissue."
In an accompanying commentary, stem cell research pioneer J. Hescheler of the University of Cologne (Cologne, Germany) said the Israeli study "provides the first compelling evidence that human embryonic stem cells can be differentiated into cardiomyocytes," and cited the possibility of using such cells "as a source for cell replacement or growing organ tissue ... for transplantation after heart injury."