The dream of cardiologists is to have stockpiles of cardiac progenitor cells that could be transplanted into a sick heart and regenerate it. Even more remarkable would be a source of heart cells for newborn babies with congenital heart problems. What about making these cells before they are born? Science fiction?
Probably not. Dr. Shaun M. Kunisaki from Mott Children’s Hospital and the University of Michigan School of Medicine and his colleagues made heart progenitor cells from Amniotic Fluid Cells. These cells were acquired from routine amniocentesis procedures, with proper institutional review board approval.
These amniotic fluid specimens (8–10 ml), which were taken from babies at 20 weeks gestation, were expanded in culture and then reprogrammed toward pluripotency using nonintegrating Sendai virus (SeV) vectors that expressed the four commonly-used reprogramming genes; OCT4, SOX2, cMYC, and KLF4. The resulted induced pluripotent stem cell (iPSC) lines were then exposed to cardiogenic differentiation conditions in order to generate spontaneously beating amniotic fluid-derived cardiomyocytes (AF-CMs). AF-CMs were formed with high efficiency.
After 6 weeks, Kunisaki and his team subjected their AF-CMs to a battery of quantitative gene expression experiments. They discovered that their AF-CMs expressed high levels of heart-specific genes (including MYH6, MYL7, TNNT2, TTN, and HCN4). However, Kunisaki and others also found that their AF-CMs consisted of a mixed population of differentiated atrial, ventricular, and nodal cells, as demonstrated by various genes expression profiles.
All AF-CMs were chromosomally normal and had no remnants of the SeV transgenes. Functional characterization of these AF-CMs showed a higher spontaneous beat frequency in comparison with heart cells made from dermal fibroblasts. The AF-CMs also showed normal calcium currents and appropriately responded to neurotransmitters that usually speed up the heart, like norepinephrine.
Collectively, these data suggest that human amniotic fluid-derived cells can be used to produce highly scalable sources of functional, transgene-free, autologous heart cells before child is born. Such an approach may be ideally suited for patients with prenatally diagnosed cardiac anomalies.