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Project aims to accomplish cell-based heart repair

New cells for the diseased heart
Looking to repair heart damage with cultured heart muscle cells: Dr Robert Zweigerdt (left) and Professor Dr Ulrich Martin Credit: Karin Kaiser / MHH

Chronic heart failurealso referred to as cardiac insufficiency in medicineis the most typical reason behind hospital admissions and something of the very most frequent factors behind death under western culture. In Germany alone, 4 million people have problems with this disease. Ordinarily a coronary attack precedes heart failure.

A global research team led by Dr. Robert Zweigerdt, at the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO) at the Hannover Medical School (MHH) and LEBAO director Professor Dr. Ulrich Martin, now desire to create a where damaged tissue areas could be repaired by using small cell clusters of biotechnologically produced heart muscle cells. Their work is area of the HEAL project, that involves 10 partners from around Europe and Israel.

Bringing heart muscle cells to the prospective

In lots of heart diseases, arteries are damaged. Consequently, the undersupplied heart muscle cells (cardiomyocytes) die. Scar tissue formation forms and heart function is impaired. Unlike in a few amphibians and fish species, such damage isn’t repaired within an adult human heart. Scientists all over the world are therefore focusing on ways of replace destroyed heart tissue. One promising approach uses so-called induced (iPS cells). These iPS cells could be stated in the laboratory from “reprogrammed” cells of adults and will then bring about any cell kind of the human bodyincluding heart muscle cells.

Along with producing such cardiomyocytes from iPS cells in the clinically required quantity and quality, another major challenge would be to obtain the cells in to the heart in a manner that they attach well and improve cardiac muscle function in harmony with the organ all together. One option would be to inject the iPS cardiomyocytes straight into the damaged heart muscle.

“The big disadvantage is that lots of cells are lost on the way and just a few survive and growespecially if isolated cells are employed,” says Dr. Zweigerdt. Another approach would be to first create a tissue construct from the and insert it surgically. However, this technique can only just treat injury on the organ surface.

New strategy with small cell clusters

The HEAL research team is therefore pursuing a fresh strategy. “Although we also depend on iPS cardiomyocytes, you want to grow them into cell aggregates already during production in the laboratory,” explains the scientist. In special bioreactors, large levels of these spherical cell aggregates should be produced, that will not be lost so quickly, will stay there better after injection in to the heart tissue and really should survive.

“We are able to grow aggregates of different sizes as needed, however they remain small enough to be administered having an injection in to the desired region of the center,” says Dr. Zweigerdt. The researchers were already in a position to successfully prove that the cell clumps actually grow in the center tissue and improve organ function in animal models within the iCARE project coordinated by Professor Martin. In the brand new research study HEAL, the approaches for producing and administering the iPS cardiomyocyte aggregates are actually to be refined so they can also be utilized for heart therapy in humans.

Suicide gene to avoid tumor formation

This goal presents the HEAL team with very special challenges. On the main one hand, the iPS cells should be adapted so that the cells created from them cause as few defense reactions as you possibly can after administration in to the body, so the only needs to be kept in balance to a extent with drugs. Secondly, the cells should be particularly safe.

“They need to not trigger cardiac arrhythmias in the center, nor must they degenerate into tumors,” explains the cell biologist. The researchers desire to investigate the possible side-effect of arrhythmias in a big animal model, which reacts particularly sensitively to disturbances due to the foreign cardiomyocytes. The researchers desire to banish the chance of unwanted tumor formation by using a genetic trick. “We create a suicide gene in to the iPS cells which can be activated if the applied cells degenerate in your body,” says Professor Martin.

“Ultimately, you want to produce safe cell products that may also be produced on a big scale in extra-large bioreactors under sterile conditions in the clean room,” says Dr. Zweigerdt. The goal is to create the conditions now so the new heart therapy can benefit as much patients as you possibly can later on.

“This technique has to meet up with the high standards required of a cell product for clinical use,” says Professor Martin. Regulatory authorities like the Paul Ehrlich Institute are monitoring the four-year project. If everything goes as planned, the researchers hope, prerequisites for a clinical trial of cell-based heart repair in humans can subsequently be met.



Provided byMedizinische Hochschule Hannover

Citation: Project aims to accomplish cell-based heart repair (2022, September 2) retrieved 4 September 2022 from https://medicalxpress.com/news/2022-09-aims-cell-based-heart.html

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