Researchers at the University of Columbia (USA) have manufactured the first human heart muscle from stem cells that has the fundamental characteristics of the functioning of the adult human heart. Researchers have stimulated induced pluripotent stem cells (iPS) through electrical and mechanical stimulation at an early stage.
The authors emphasize that the possibility of generating human heart tissue that behaves like the native heart muscle would be "transformative" for biomedical research, since it would allow researchers to study human physiology and cardiovascular diseases under fully controlled conditions.
Stem cells have the potential to develop into many different types of cells. However, human cells lose this capacity once they have matured, which is why, for example, the cells of the heart do not spontaneously decide to become lung cells. Induced pluripotent stem cells are cells obtained from an adult that have been manipulated, or induced, into a state of stem cells.
Researchers can direct these cells to different types of cells through various chemical and physical stimuli. On this occasion, scientists have been able to design cardiac tissue using cardiomyocytes derived from iPS. However, obtaining a designed tissue that can successfully imitate the complexities of adult human heart cells is not easy and, so far, has not been achieved in the laboratory.
To achieve this, explains Gordana Vunjak-Novakovi, professor of Biomedical Engineering at Columbia University. "We force the cultured heart muscle to go through the fetal to postnatal transition through accelerated development." The researchers electrically stimulated iPS stem cells at an early stage and, little by little, increased the frequency of electrically induced contractions, little by little, every day. In just four weeks of culture, "the tissues responded and showed gene expression similar to that of adults, a remarkably organized structure and a series of functional features seen in the mature heart muscle." This approach, they say, is radically new, since the time frame for muscle development has been compressed, since it usually takes nine months.
The other important advance of this study is that, instead of the gentle mechanical stretching that is present in a developing fetal heart, the researchers applied a special electromechanical conditioning regimen, gradually increasing the frequency of electrically induced contractions every day. This regime forced the cultivated muscle to work, every day, harder than the previous one. The goal was to see if the redesigned heart would respond as a "native" heart by gradually accommodating the increased load and making the transition from fetal to postnatal.
The technique worked. The researchers saw comprehensive changes at all levels, which led to a rapid and unprecedented maturation of tissue structure, metabolism and function. In only four weeks of cultivation, they affirm:
"the tissues showed similar gene expression profiles to adults, remarkably organized ultrastructure and a series of functional characteristics seen in the mature human heart muscle"
The physiological length of the sarcomere (contractile machinery of the cell); physiological density of mitochondria (cellular energy factory); presence of transverse tubules (critical characteristics, previously undocumented, of the cell membrane that help the cell to respond rapidly to changes in calcium and transmit signals), and the change to oxidative metabolism and functional calcium management.