Stem cell technology:

Researchers have succeeded in creating new diaphragm tissue in rats using stem cell technology. The success creates hope of being able to repair congenital malformations of the diaphragm in infants. The researchers also believe in opportunities to repair damaged heart tissue with the same technology in the future.

An international multidisciplinary research team has caused stem cells to grow on a three-dimensional biological framework which, when transplanted and integrated into the body, exhibited the same complex function as a diaphragm muscle.

The diaphragm consists of muscle layers which, because of the breathing, must constantly contract (contract) and relax. The diaphragm also has an important function when swallowing and acts as a barrier between the thorax and the abdomen. In 1 in 2,500 newborns, malformations occur in the form of holes in the diaphragm, which can cause very severe or life-threatening conditions.

Biological Transplantation

At present, such malformations are remedied during surgery, using an artificial material that does not follow the baby’s growth and cannot contract to support breathing. According to the researchers, the new technology that is now being presented inspires hope to be able to repair damaged diaphragm with a biological transplant developed from the children’s own cells. The graft can be designed specifically for infants and provide the same function as normal diaphragm tissue and also grow when the baby grows.

Creating a working muscle with biotechnology is an exciting step towards our goal of recreating whole and complex organs, says Paolo Macchiarini. The result of this study also gives hope for future opportunities to repair damaged heart tissue, which, like a diaphragm, is continuously tensioned and relaxed. I also think there is potential in the future to create whole organs with this technology.

Grow new organs

Part of the research in regenerative medicine is about “cultivating” new organs where stem cells are attached to three-dimensional frames. These provide structure and shape for the new tissue and act as a kind of guide for the development and spread of new cells on the surface. The ultimate potential of this stem cell-based therapy is to avoid lifelong treatment with immunosuppressive drugs used in conventional organ transplantation.

In the current study, the researchers took rats diaphragm tissue and removed all living cells from it. In this way, you remove what can cause rejection in the recipient animal while at the same time getting a body with the right shape and structure that the stem cells can then grow on. In laboratory experiments, the decellularized bodies appeared to have initially lost the elasticity required for the diaphragm to contract and relax for a long time. But when the frames were then covered with stem cells from bone marrow, and allowed to integrate with the recipient’s tissue, the grafts worked as well as healthy organs.

Hard growing diaphragm:

So far, attempts at growing and transplanting new tissue have been performed on less complicated organs such as bladder, trachea and esophagus. Creating new muscle tissue on a diaphragm, which must constantly switch between contraction and relaxation, places considerably higher demands on the body on which the cells are to grow. Until now, no one has known if it would work, says Doris Taylor, research director of regenerative medicine at the Texas Heart Institute in Houston.

Now, research on larger animals is required before the method can be tested on humans. But the hope is that with cultured tissue, it will be possible to repair congenital malformations of diaphragms at least as efficiently as with today’s surgery where artificial materials are used, but with the advantage that the graft follows the child’s growth throughout life.

The study was funded by funds from the Bioengineering of Tracheal Tissue and The Government of the Russian Federation Grant.

The international multidisciplinary research team has been led by Paolo Macchiarini, senior researcher in regenerative medicine at Karolinska Institutet. The collaboration includes researchers from Kuban State Medical University in Krasnodar Russia, the Texas Heart Institute in Houston and the Illinois College of Medicine in Peoria, USA.

For further information

Paolo Macchiarini, MD, PhD, Karolinska Institutet. Tel: +46 76-050 32 13