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Topic Name: Researchers Create Beating Heart in Laboratory Using Organ Decellularization Process

Category: Biomedical

Research persons: Doris Taylor, Ph.D.

Location: University of Minnesota, United States

Details

University of Minnesota researchers have created a beating heart in the laboratory.

By using a process called whole organ decellularization, scientists from the University of Minnesota Center for Cardiovascular Repair grew functioning heart tissue by taking dead rat and pig hearts and reseeding them with a mixture of live cells. The research will be published online in the January 13 issue of Nature Medicine.

“The idea would be to develop transplantable blood vessels or whole organs that are made from your own cells,” said Doris Taylor, Ph.D., director of the Center for Cardiovascular Repair, Medtronic Bakken professor of medicine and physiology, and principal investigator of the research.

Nearly 5 million people live with heart failure, and about 550,000 new cases are diagnosed each year in the United States. Approximately 50,000 United States patients die annually waiting for a donor heart.

While there have been advances in generating heart tissue in the lab, creating an entire 3-dimensional scaffold that mimics the complex cardiac architecture and intricacies, has always been a mystery, Taylor said.

It seems decellularization may be a solution – essentially using nature’s platform to create a bioartifical heart, she said.

Decellularization is the process of removing all of the cells from an organ – in this case an animal cadaver heart – leaving only the extracellular matrix, the framework between the cells, intact.

After successfully removing all of the cells from both rat and pig hearts, researchers injected them with a mixture of progenitor cells that came from neonatal or newborn rat hearts and placed the structure in a sterile setting in the lab to grow.

The results were very promising, Taylor said. Four days after seeding the decellularized heart scaffolds with the heart cells, contractions were observed. Eight days later, the hearts were pumping.

“Take a section of this ‘new heart’ and slice it, and cells are back in there,” Taylor said. “The cells have many of the markers we associate with the heart and seem to know how to behave like heart tissue.”

“We just took nature’s own building blocks to build a new organ,” said Harald C. Ott, M.D., co-investigator of the study and a former research associate in the center for cardiovascular repair, who now works at Massachusetts General Hospital. “When we saw the first contractions we were speechless.”

Researchers are optimistic this discovery could help increase the donor organ pool.

In general, the supply of donor organs is limited and once a heart is transplanted, individuals face life-long immunosuppression, often trading heart failure for high blood pressure, diabetes, and kidney failure, Taylor said.

Researchers hope that the decellularization process could be used to make new donor organs. Because a new heart could be filled with the recipient’s cells, researchers hypothesize it’s much less likely to be rejected by the body. And once placed in the recipient, in theory the heart would be nourished, regulated, and regenerated similar to the heart that it replaced.

“We used immature heart cells in this version, as a proof of concept. We pretty much figured heart cells in a heart matrix had to work,” Taylor said. “Going forward, our goal is to use a patient’s stem cells to build a new heart.”

Although heart repair was the first goal during research, decellularization shows promising potential to change how scientists think about engineering organs, Taylor said. “It opens a door to this notion that you can make any organ: kidney, liver, lung, pancreas – you name it and we hope we can make it,” she said.

Researchers of the Center for Cardiovascular Repair team were assisted in their study by researchers from the University of Minnesota Department of Biomedical Engineering, who helped analyze data.

The study was funded by the Medtronic Foundation Endowment and a faculty research development grant from the University of Minnesota Academic Health Center.

Note for Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions. Deliberately induced immunosuppression is generally done to prevent the body from rejecting an organ transplant, treating graft-versus-host disease after a bone marrow transplant, or for the treatment of auto-immune diseases such as rheumatoid arthritis or Crohn's disease. This is typically done using drugs, but may involve surgery (splenectomy), plasmapharesis, or radiation.
A person who is undergoing immunosuppression, or whose immune system is weak for other reasons (for example, chemotherapy and HIV patients) are said to be immunocompromised. When an organ is transplanted, the immune system of the recipient will most likely recognize it as foreign tissue and attack it. The destruction of the organ will, if untreated, end in the death of the recipient.
In the past, radiation therapy was used to decrease the strength of the immune system, but now immunosuppressant drugs are used to inhibit the reaction of the immune system. The downside is that with such a deactivated immune system, the body is very vulnerable to opportunistic infections, even those usually considered harmless. Also, prolonged use of immunosuppressants increases the risk of cancer.

Note for Cardiovascular Disease
Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels (arteries and veins). While the term technically refers to any disease that affects the cardiovascular system, it is usually used to refer to those related to atherosclerosis (arterial disease). These conditions have similar causes, mechanisms, and treatments. In practice, cardiovascular disease is treated by cardiologists, thoracic surgeons, vascular surgeons, neurologists, and interventional radiologists, depending on the organ system that is being treated. There is considerable overlap in the specialties, and it is common for certain procedures to be performed by different types of specialists in the same hospital.
Most Western countries face high and increasing rates of cardiovascular disease. Each year, heart disease kills more Americans than cancer. Diseases of the heart alone caused 30% of all deaths, with other diseases of the cardiovascular system causing substantial further death and disability. Up until the year 2005, it was the number 1 cause of death and disability in the United States and most European countries. A large histological study (PDAY) showed vascular injury accumulates from adolescence, making primary prevention efforts necessary from childhood.