Scientists grow the first functioning mini human heart model
Scientists grow the first
functioning mini human heart model
by Kim Ward, Michigan State University August 21,
2020
Michigan State University
researchers have created for the first time a miniature human heart model in
the laboratory, complete with all primary heart cell types and a functioning
structure of chambers and vascular tissue.
In the United States, heart disease is
the No. 1 cause of death. "These minihearts constitute incredibly powerful
models in which to study all kinds of cardiac disorders with a degree of
precision unseen before," said Aitor Aguirre, the study's senior author
and assistant professor of biomedical engineering at MSU's Institute for
Quantitative Health Science and Engineering.
This study, "Generation
of Heart Organoids Modeling Early Human Cardiac Development Under Defined
Conditions," appears on the bioRxiv preprint server.
The human heart organoids, or hHOs
for short, were created by way of a novel stem cell framework that mimics the
embryonic and fetal developmental environments.
"Organoids—meaning
'resembling an organ'—are self-assembling 3-D cell constructs that recapitulate
organ properties and structure to a significant extent," said Yonatan
Israeli, a graduate student in the Aguirre Lab and first author of the study.
The innovation deploys a
bioengineering process that uses induced pluripotent stem
cells—adult cells from
a patient to trigger embryonic-like heart development in a dish—generating a
functional mini heart after a few weeks. The stem cells are obtained from
consenting adults and therefore free of ethical concerns.
"This process allows the
stem cells to develop, basically as they would in an embryo, into the various
cell types and structures present in the heart," Aguirre said. "We
give the cells the instructions and they know what they have to do when all the
appropriate conditions are met."
Because the organoids
followed the natural cardiac embryonic development process, the researchers
studied, in real time, the natural growth of an actual fetal human heart.
This technology allows for
the creation of numerous hHOs simultaneously with relative ease, contrasting
with existing tissue engineering approaches that are expensive, labor intensive
and not readily scalable.
One of the primary issues
facing the study of fetal heart development and congenital heart defects is
access to a developing heart. Researchers have been confined to the use of
mammalian models, donated fetal remains and in vitro cell research to
approximate function and development.
"Now we can have the
best of both worlds, a precise human model to study these diseases—a tiny human
heart—without using fetal material or violating ethical principles. This
constitutes a great step forward," Aguirre said.
What's next? For Aguirre, the
process is twofold. First, the heart organoid represents an
unprecedented look into the nuts and bolts of how a fetal heart develops.
"In the lab, we are
currently using heart organoids to model congenital heart disease—the most
common birth defect in humans affecting nearly 1% of the newborn
population," Aguirre said. "With our heart organoids, we can study
the origin of congenital heart disease and find ways to stop it."
And second, while the hHO is
complex, it is far from perfect. For the team, improving the final organoid is
another key avenue of future research. "The organoids are small models of
the fetal heart with representative functional and structural features,"
Israeli said. "They are, however, not as perfect as a human heart yet.
That is something we are working toward."
Aguirre and team are excited
about the wide-ranging applicability of these miniature hearts. They enable an
unprecedented ability to study many other cardiovascular-related diseases—from
chemotherapy-induced cardiotoxicity to the effect of diabetes, during
pregnancy, on the developing fetal heart.
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