Human-based alternatives to animal models are being developed worldwide, due to the increasing need for more relevant biological systems.
Researchers at Michigan State University (MSU) have grown the first
functioning mini human heart model. As discussed in a recently published
study, the model includes all the primary heart cell types, as well as
functioning chamber structures and vascular tissue. I had the opportunity to
have a virtual sit down with Aitor Aguirre, the senior author of the study
and assistant professor of biomedical engineering in MSU’s Institute for
Quantitative Health Science and Engineering and Principal Investigator of
the Aguirre Lab.
Dr. Aguirre has both a M.S. in Biochemistry and Molecular Biology from the
University of the Basque Country in Spain and a Ph.D. in Materials Science
and Tissue Engineering from the Institute for Bioengineering of Catalonia
and the Technical University of Catalonia. Additionally, he worked on
genetic mechanisms of cell dedifferentiation, cardiac regeneration, and
human development as a postdoc with the Salk Institute. The Aguirre Lab at
MSU uses human stem cells to investigate the control pathways in cell
reprograming, development, and regeneration. The mini human heart study,
“Generation of Heart Organoids Modeling Early Human Cardiac Development
Under Defined Conditions” can be found in bioRxiv and was funded by grants
from the National Institute of Health and the American Heart Association.
Aguirre has been thinking about human-centered technology and heart
organoids since his postdoc in 2011. When he established the Aguirre lab,
using stem cells with a focus on cardiac systems, his first endeavor was to
create heart organoids. These organoids or mini hearts are created by
bioengineering adult stem cells from a patient into functional mini heart
within a few weeks by kick-starting “embryonic-like heart development in a
dish.” The heart organoids are currently being used to study adult cardiac
disorders, toxicity, cancer development, and pharmacological research and
development. However, Aguirre is currently refining the organoids to better
model disorders like heart disease, the leading cause of death in the United
States.
Aguirre is also using the heart models to study congenital heart defects. He
noted that congenital heart defects affect about 1% of newborn population,
while diseases such as diabetes during pregnancy can increase the risk of a
congenital defects to 12%. Using the organoids presents the ability to more
accurately learn about these defects and the risks in ways that cannot be
learned from animal models, due to intractable interspecies difference in
cardiac morphology, biochemistry, and function.
Stem cell models are scientific game changers because they have the ability
to divide and produce new cells and change into other specialized types of
cells that make up the body, as well as can be used to grow specific tissue
types or organs. According to Aguirre “almost everything we know about
[cardiac] systems come from mice, but we know that mice do things
differently during development and that they do not really model humans.”
Previously, there has been ethical concerns about working with stem cells,
but the concerns do not really exist anymore due to consenting adult stem
cell donors. Aguirre stated “working on animals is becoming less relevant
now that we have access to human systems” and now we have the tools to work
on human systems without the ethical concerns that existed before.
Using human models allows for lines of investigation that would be not be
possible with animal models. An example provided by Aguirre is typically by
the time a doctor is able to diagnose someone with heart disease, the
patient has already had the disease for years, but in vitro modeling can
show the early stages of disease progression in humans in ways animal models
cannot, and therefore can help us to prevent or treat the disease from the
start.
Human-based alternatives to animal models are being developed worldwide, due
to the increasing need for more relevant biological systems. Aguirre hopes
that these systems (such as organoids) will be implemented in pharmaceutical
testing in place of animals, which would greatly improve drug development
success rates. Currently there is more than 90% failure rate in drug
development in large part because animal tests do not accurately predict
safety and efficacy in humans. Additionally, Aguirre hopes to collaborate
with other researchers at MSU so that they may make use of his human models
rather than continue with animal models.
Moving forward Aguirre hopes that these systems will be implemented to a
great extent and that testing and research will be much more human-centered
rather than animal model focused. He believes that the advantages offered by
technology like organoids over animals is large and thinks that there should
be more grants and incentives offered to researchers and pharmaceutical
companies to help human-centered models become the norm. Aguirre plans to
continue to refine his models to be as sophisticated as possible by creating
active circulation around his heart organoids and trying to model a
cardiopulmonary system.
Return to Alternatives to Animal Testing, Experimentation and Dissection