Human Amniotic Fluid Stem Cells Can Act Like Heart Cells, Sort of

Human amniotic fluid-derived stem cells (AFSC) have a demonstrated ability to differentiate into several different adult cell types, and they also fail to form tumors in laboratory animals.

A previous study of AFSCs showed that if these stem cells were grown in culture with heart muscle cells from newly born rats, the AFSCs began to express heart-specific genes. While the AFSCs did not become full-fledged heart muscle cells, they began to differentiate in that direction.

Yang Gao and others in the laboratory of Jeffrey G. Jacot at Rice University tried this same experiment with human heart cells. They used a specific set of cell culture conditions that prevent the AFSCs from fusing with the heart cells, because the fusion of two cells can deceive researchers into thinking that the stem cells have actually become heart cells when in fact they have not.

Jacot and his coworkers discovered that when human AFSC made contact with human heart cells, they began to express proteins normally found in heart muscle that help them contract. One of these proteins, cardiac troponin T (cTnT), was definitely expressed in human AFSCs, even though this protein is rather specific to heart muscle cells. cTnT is also one of the proteins released into the bloodstream after a heart attack.  Further investigation uncovered absolutely no evidence of cell fusion. Thus when AFSCs touch human heart cells, they begin to make some heart-specific proteins.

Cardiac Troponin

Jacot and his group did an additional experiment. They tried culturing the human AFSCs on one side of the porous membrane and human heart cells on the other side. These conditions allow minimal contact between cells, but still exposes them the anything the cells might be secreting. Under these culture conditions, human AFSCs still showed a statistically significant increase in cTnT expression compared to culture conditions that without contact between the two cell types.  However, human AFSCs grown in the present of human heart cells still did not express the calcium modulating proteins that are so important for regulating heart muscle contraction. Additionally, the cells and did not have functional or morphological characteristics of mature heart muscle cells.

These data suggest that contact between heart cells and human AFSCs is a necessary but not sufficient condition to drive AFSCs to differentiate into heart cells. However, touching heart cells gets AFSCs part of the way. Maybe further research will provide other cues that will push these remarkable cells the rest of the way.

Biowire Technology Matures Stem Cell-Derived Heart Cells

Heart research has taken yet another step forward with the invention of a new technique for maturing human heart cells in culture.

Researchers from the University of Toronto have created a fast and reliable method of creating mature human heart muscle patches in a variety of sizes. This technique applies pulsed electric current to the cells that mimics the heart rate of fetal humans.

Milica Radisic, an associate professor at the Institute of Biomaterials and Biomedical Engineering (IBBME), explained the significance of her new discovery: “You cannot obtain human cardiomyocytes (heart cells) from human patients.” However heart cells are vitally important for testing the safety and efficacy of heart drugs, and because human heart muscle cells do not normally divide robustly and form large swaths of heart tissue in culture, finding enough human heart tissue for pharmacological and toxicological test tests has been rather difficult. Tho circumvent this problem, researchers have been using heart muscle cells made from induced pluripotent stem cells (iPSCs). Unfortunately, once these cells are differentiated into heart muscle cells, they form highly immature heart muscle cells that beat too fast to work as a proper model system for adult human heart cells.

As Radisic put it: “The question is, if you want to test drugs or treat adult patients, do you want to use cells that look and function like fetal cardiomyocytes? Can we mature these cells to become more like adult cells?”

Radisic and her co-workers designed the “biowire” culture system for stem cell-derived cardiomyocytes. This system can mature heart muscle cells in culture in a reliable and reproducible manner.

The technique seeds human heart muscle cells along a silk suture, much like the kind used to sew up patients after surgery. The suture directs cells to grow along its length, after which they a treated to cycles of electric pulses. The biowire provides the pulses and acts like a stripped-down pacemaker. The biowire induces the heart muscle cells to increase in size and beat like more mature heart tissue. However the manner in shich the pulses are applied turns out to be very important. Radisic and her team discovered that if the cells were ramped up from zero pulses to 180 pulses per minute to 360 beats per minute, it mimicked the conditions that occur naturally in the developing heart. The fetal heart increases its heart rate prior to birth, and by ramping up the rate at which the pulses were delivered, Radisic and her team exposed the heart cells to the same kind of environment they would have experienced in the fetal heart.

“We found that pushing the cells to their limits over the course of a week derived the best effect,” said Radisic.

Growing the cells on sutures brings an added bonus: They can be sewn directly into a patient, which makes the biowires fully transplantable. Also, the cells can be grown on biodegradable sutures as well, which has practical implications for health care.

“With this discovery we can reduce the costs on the health care system by creating more accurate drug screening.” This discovery brings heart research one step closer to viable heart patches for replacing dead areas of the heart.

The paper’s first author, Sarah Nunes, said this: “One of the greatest challenges of tgransplanting these patches is getting the cells to survive, and for that they need blood vessels. Our next challenge is to put the vascularization together with cardiac cells.” Nunes is a cardiac and a vascular specialist.

Radisic enthusiastically labeled the new technique as a “game changer” in the field of cardiac medicine and it is a sign of how far the field has come in a very short time.

“In 2006 science saw the first derivation of induced pluripotent stem cells from mice. Now we can turn stem cells into cardiac cells and make relatively mature tissue from human samples, without ethical concerns.”

The vascularization part of this should be rather easy, since bone marrow-derived endothelial progenitor cells (EPCs) have been shown to make blood vessels in the heart. Putting these together with the heart patch should provide a winning combination

Inching toward human trials, but definitely making progress!!