Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Therapeutic advancement in search for heart muscle progenitor cells – hope for heart attack patients

19.11.2012
Breakthrough in heart research: The research team from Professor Katja Schenke-Layland of the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB in Stuttgart has discovered cell surface markers that enable the identification and isolation of living functional cardiovascular progenitor cells (CPCs).
For the first time, therapeutically relevant CPCs can be derived from induced-pluripotent stem cells (iPS) cells. CPCs, which are typically only found in fetal development, can become all of the different cell types of the heart and can integrate into heart muscle tissue after injection.

An estimated 17 million people die from cardiovascular disease each year. Although mortality rates are declining, heart attacks are still among the most frequent causes of death in the developed world. Often, the cause of a heart attack is the closure of a coronary artery that supplies blood to the heart, which kills heart muscle cells. Cardiomyocytes, which are the heart muscle cells responsible for the contraction of the heart, are not able to regenerate after a heart attack. The massive loss of cells and tissue, and the highly restricted regeneration capacity of the adult heart, lead to an impaired blood supply throughout the body that drastically affects a patient’s quality of life. To restore the heart’s function after a major heart attack, clinicians require functionally mature cardiomyocytes that perform like the native cells in the adult heart to replace the cells that were killed.

The production of such functional cardiomyocytes from well-defined cardiovascular progenitor cells (CPCs) is the focus of the research team led by Prof. Dr. Katja Schenke-Layland from the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB in Stuttgart and her colleagues, Dr. Ali Nsair of the University of California Los Angeles (UCLA) and Prof. Dr. Robb MacLellan of the University of Washington in Seattle, who have now succeeded in identifying such cells in a mouse model. The work, which could revolutionize the treatment of heart disease, was recently published in the journal PLoS ONE (PLoS ONE7 (10):e45603, doi:10.1371/journal.pone.0045603).

Development of heart muscle cells from precursor cells

Myocardial cells – as well as endothelial cells and smooth muscle cells – develop from CPCs during the embryonic development of humans and other animals. There has been a significant amount of research effort towards discovering a path for the clinical application of these cells in patients. The reason for the lack of success is that the markers that help to identify CPCs, such as Islet1 or Nkx2.5, are located in the nucleus of the cells. The use of these cell markers modifies the cells rendering them therapeutically unusable, making the identification of safe cell-surface markers essential.

Surface markers identified for cardiovascular progenitor cells

On this task, the research team of Professor Katja Schenke-Layland from the Fraunhofer IGB in Stuttgart, Prof. Dr. Robb MacLellan and Dr. Ali Nsair of the University of California Los Angeles (UCLA), where Schenke-Layland previously worked before returning to Germany to join the Fraunhofer-Gesellschaft’s Attract Program, focused their research. With success: They were able to identify two markers, the receptors Flt1 (VEGFR1) and Flt4 (VEGFR3), on the surface of CPCs with which these cells can be clearly identified while fully preserving their biological function. This discovery allows scientists to isolate clinically relevant cardiovascular progenitor cells that can be functionally matured.

In the search for surface markers, the researchers investigated the cardiovascular progenitor cells using microarray gene expression profiling. These studies show exactly which genes are active at a specific point in time. The resulting data from this analysis were compared to the sequencing data from existing databases of already known as cell markers.
From induced-pluripotent stem cells, cardiovascular progenitor cells are developed

Encouraged by the success of being able to identify and isolate living CPCs, the researchers sought out to derive the cells from induced-pluripotent stem (iPS) cells. For this purpose, they used a method for which the Japanese scientist Shinya Yamanaka was recently awarded the 2012 Nobel Prize for Medicine. This work, published just six years ago, demonstrated that only four proteins are responsible for the embryonic state of cells (Takahashi K, Yamanaka S. Cell 2006, 126 (4): 663 -676). He brought those four genes into differentiated – mature and specialized – cells, which then returned them back to an embryonic state. From these cells, which he called iPS cells, scientists can develop all cells of the body, such as liver cells, nerve cells or heart muscle cells.

In their study, the researchers used cells from a mouse strain in which the cells are labeled with a visible green fluorescent protein (GFP) that can be identified with a fluorescence microscope. The cells from these mice were then reprogrammed with the same four genes discovered by Yamanka, resulting in iPS cells that could be easily identified.

In a next step, the researchers cultured the GFP-labeled iPS cells in the laboratory under different conditions with cell-influencing solutions such as growth factors. "Using our newly established cell surface markers, we could detect and isolate the Flt1 and Flt4 positive CPCs in culture," says Schenke-Layland. "When we cultured the isolated mouse CPCs then in vitro, they actually developed – as well as the embryonic stem cell-derived progenitor cells – into endothelial cells, smooth muscle cells and more interestingly into functional heart muscle cells."

iPS cell-derived CPCs integrate into the living mouse heart

But how do the developed CPCs behave in living organisms? Can these cells really integrate into tissue and regenerate heart muscle? To answer these questions, the scientists injected the GFP-labeled CPCs into the hearts of living mice. After 28 days, the researchers analyzed the hearts and saw that the green fluorescent cells had developed into beating heart muscle cells and had fully integrated into the myocardial tissue of the mouse.

Enormous potential for heart research

Researchers have long tried to stimulate the regeneration of heart muscle cells. For this purpose, they inject stem cells or stem cell-derived cardiomyocytes into the heart. Although the majority of studies found a slight improvement in heart function, in most cases, neither long-term integration nor the differentiation of the cells into heart muscle has been demonstrated.

The result of the group from Schenke-Layland, Nsair and MacLellan provides the first opportunity to generate functioning heart muscle cells, which integrate into the heart muscle. "We are currently focusing on research with human iPS cells. If we can show that cardiovascular progenitor cells can be derived from human iPS cells that have the ability to mature into functional heart muscle, we will have discovered a truly therapeudic solution for heart attack patients", hopes the scientist.

Funding

The work of the research group has been funded by the German-American funding from the Federal Ministry of Education and Research (BMBF) and the California Institute for Regenerative Medicine (CIRM), as well as the Fraunhofer-Gesellschaft (Attract Program), the Ministry of Science, Research and the Arts of Baden-Württemberg, and the US National Institutes of Health (NIH).

Contact
Professor Katja Schenke-Layland
Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB
Nobelstrasse 12, 70569 Stuttgart, Germany
Phone +49 711 970-4082

Dr. Claudia Vorbeck | Fraunhofer-Institut
Further information:
http://www.igb.fraunhofer.de/en/press-media/press-releases/2012/CPCs-from-iPS-cells.html

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Speed data for the brain’s navigation system

06.12.2016 | Health and Medicine

What happens in the cell nucleus after fertilization

06.12.2016 | Life Sciences

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>