A miniature heart in a petri dish: Organoid emulates development of the
human heart

Date:
April 4, 2023
Source:
Technical University of Munich (TUM)
Summary:
A team has induced stem cells to emulate the development of the
human heart. The result is a sort of 'mini-heart' known as an
organoid. It will permit the study of the earliest development
phase of our heart and facilitate research on diseases.


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FULL STORY ==========================================================================
A team at the Technical University of Munich (TUM) has induced stem
cells to emulate the development of the human heart. The result is a
sort of "mini- heart" known as an organoid. It will permit the study
of the earliest development phase of our heart and facilitate research
on diseases.


==========================================================================
The human heart starts forming approximately three weeks after
conception. This places the early phase of heart development in a time
when women are often still unaware of their pregnancy. That is one reason
why we still have little knowledge of many details of how the heart
is formed. Findings from animal studies are not fully transferable to
humans. An organoid developed at TUM could prove helpful to researchers.

A ball of 35,000 cells The team working with Alessandra Moretti, Professor
of Regenerative Medicine in Cardiovascular Disease, has developed a method
for making a sort of "mini- heart" using pluripotent stem cells. Around
35,000 cells are spun into a sphere in a centrifuge. Over a period
of several weeks, different signaling molecules are added to the cell
culture under a fixed protocol. "In this way, we mimic the signaling
pathways in the body that control the developmental program for the
heart," explains Alessandra Moretti. The group has now published its
work in the journal Nature Biotechnology.

First-ever "epicardioids" The resulting organoids are about half a
millimeter in diameter. Although they do not pump blood, they can be
stimulated electrically and are capable of contracting like human heart chambers. Prof. Moretti and her team are the first researchers in the
world to successfully create an organoid containing both heart muscle
cells (cardiomyocytes) and cells of the outer layer of the heart wall (epicardium). In the young history of heart organoids -- the first were described in 2021 -- researchers had previously created only organoids
with cardiomyocytes and cells from the inner layer of the heart wall (endocardium).

"To understand how the heart is formed, epicardium cells are decisive,"
says Dr. Anna Meier, first author of the study. "Other cell types in the
heart, for example in connecting tissues and blood vessels, are formed
from these cells.

The epicardium also plays a very important role in forming the
heart chambers." The team has appropriately named the new organoids "epicardioids." New cell type discovered Along with the method
for producing the organoids, the team has reported its first new
discoveries. Through the analysis of individual cells they have determined
that precursor cells of a type only recently discovered in mice are
formed around the seventh day of the development of the organoid. The epicardium is formed from these cells. "We assume that these cells also
exist in the human body -- if only for a few days," says Prof. Moretti.

These insights may also offer clues as to why the fetal heart can
repair itself, a capability almost entirely absent in the heart of an
adult human.

This knowledge could help to find new treatment methods for heart attacks
and other conditions.

Producing "personalized organoids" The team also showed that the organoids
can be used to investigate the illnesses of individual patients. Using pluripotent stem cells from a patient suffering from Noonan syndrome,
the researchers produced organoids that emulated characteristics of
the condition in a Petri dish. Over the coming months the team plans to
use comparable personalized organoids to investigate other congenital
heart defects.

With the possibility of emulating heart conditions in organoids, drugs
could be tested directly on them in the future. "It is conceivable that
such tests could reduce the need for animal experiments when developing
drugs," says Alessandra Moretti.

Organoid research is a key research area at TUM The researchers
have registered an international patent for the process of creating
heart organoids. The Epicardioid model is one of several organoid
projects at TUM. At the Center for Organoid Systems work groups from
various departments and chairs will collaborate. They will conduct interdisciplinary research into pancreas, brain and heart organoids with state-of-the-art imaging and cellular analysis to study the formation
of organs, cancer and neurodegenerative diseases and achieve progress
for medicine with human 3D systems.

* RELATED_TOPICS
o Health_&_Medicine
# Heart_Disease # Vioxx # Stroke_Prevention # Stem_Cells
o Matter_&_Energy
# Biochemistry # Batteries # Solar_Energy # Graphene
* RELATED_TERMS
o Heart_rate o Artificial_heart o Coronary_heart_disease o
Embryonic_stem_cell o Ischaemic_heart_disease o Defibrillation
o CPR o Artery

========================================================================== Story Source: Materials provided by
Technical_University_of_Munich_(TUM). Note: Content may be edited for
style and length.


========================================================================== Journal References:
1. Anna B. Meier, Dorota Zawada, Maria Teresa De Angelis, Laura
D. Martens,
Gianluca Santamaria, Sophie Zengerle, Monika Nowak-Imialek,
Jessica Kornherr, Fangfang Zhang, Qinghai Tian, Cordula M. Wolf,
Christian Kupatt, Makoto Sahara, Peter Lipp, Fabian J. Theis,
Julien Gagneur, Alexander Goedel, Karl-Ludwig Laugwitz, Tatjana
Dorn, Alessandra Moretti.

Epicardioid single-cell genomics uncovers principles of human
epicardium biology in heart development and disease. Nature
Biotechnology, 2023; DOI: 10.1038/s41587-023-01718-7
2. Dorota Zawada, Jessica Kornherr, Anna B. Meier, Gianluca Santamaria,
Tatjana Dorn, Monika Nowak-Imialek, Daniel Ortmann, Fangfang
Zhang, Mark Lachmann, Martina Dressen, Mariaestela Ortiz, Victoria
L. Mascetti, Stephen C. Harmer, Muriel Nobles, Andrew Tinker, Maria
Teresa De Angelis, Roger A. Pedersen, Phillip Grote, Karl-Ludwig
Laugwitz, Alessandra Moretti, Alexander Goedel. Retinoic acid
signaling modulation guides in vitro specification of human heart
field-specific progenitor pools.

Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-36764-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/04/230404114235.htm

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