Leverage in Transplantation Medicine

20. April 2007
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At first glance yet another message of success without any practical aspect - at second glance a little sensation: For the first time, scientists succeeded to suppress the natural repulsion reaction in mice with a heart transplant - without using drugs. A milestone on the roadmap of the rapidly changing transplantation medicine?

The target seems to be clearly defined, as emphasized by Matthias Gunzer, head of the working group at the Helmholtz-Zentrum für Infektionsforschung in Braunschweig. He plans to survey the procedure on humans as well. According to Gunzer, the advantages are clearly at hand. If no side effects show, when tested on humans, it means a considerable benefit for quality of life for organ beneficiaries. They would not have to take immune supressives every day to prevent the immune system to fight the new organ.

Actually various components of the human immune system are responsible for any repulsion reaction. The so-called T-effector cells play an enormous role in this, since they are the spearhead of the body's own blocking system and immediately attack any pathogens. But: The warriors of the immune system consider a newly transplanted organ as “the enemy” as well and repel it.

This is exactly the effect, the team around Gunzer was able to lever out by a molecular trick. The researchers interfered in the maturation process of the T-cells and managed to change them until the cells were no longer dangerous for the transplant. “To achieve this, we had to bring not yet matured T-cells – so-called T-assistant cells – in artificial close contact with another cell type of the immune system, the so-called B-cells”, explains Gunzer. It turned out, that, instead of immune activating T-effector cells, regulatory T-cells matured. The scientists have not found the reason for this process yet. But Gunzer knows, that “the regulatory T-cells have the contrary effect from the T-effector cells. Instead of activating the immune system, they slow down the repulsion reaction”.

They injected those regulatory T-cells resulting from B-cell contact in mice. Those animals then received a new heart. The effect is fascinating. “Theoratically, the mice should repel the heart immediately because we did not give them any immune suppressing drugs. But their immune system did accept the alien heart for a long time – without any support by drugs”, says Gunzer. “The immune system of animals without regulatory T-cells had destroyed the transplanted hearts within a few days”.

Many questions remain open

The results published in the professional journal “Blood” are an important progress in transplantation research, but the Braunschweig scientist does not want to promise quick help yet to the recipients of organ donations. Mainly because the questions regarding the functionality of the immune system have not been answered yet: Will the immune system still be able to recognize and fight pathogens after treatment with regulatory T-cells? The immense progress that the new heart or the new kidney is not repelled after transplantation will not be a very comforting one, if the immune system is not able to fight against any viruses or bacteria any more. Only if one does not exclude the other, the way is cleared to test the procedure on humans.

Until then, medicine has to rely on effective immune supressives – and is laying on spectacular accomplishments at times. Already in September 1998, the first successful hand transplantation was made in France, followed by the first double-sided transplantation in January 2000 in Lyon. Five years later, the physicians take stock: Both patients showed mild- to medium repulsion reactions, but were both treated successfully. The functionality of the hands reached more than 60 percent compared to healthy persons. Movability increased steadily during the first year and stabilized in the third year. Similar results were achieved regarding sensitivity to pain and temperature as well as the ability to grab which even kept increasing after the third year. Admittedly, the hand has advantages compared to inner organs: Repulsion reactions mainly concern the skin which can be observed directly and be treated accordingly fast.

Cardiology: Successful heart transplantation despite different blood groups

Two years ago, public witnessed a brilliant advancement in successful transplantation of inner organs. For the first time, physicians at the Klinikum Großhadern in Munich succeeded in transplanting two hearts despite different blood groups of donor and recipient. The professional world sang from the tree tops: Because the surgeries made on two infants in the age of five and seven months symbolize milestones – not only in the opinion of Heinrich Netz of Ludwig-Maximilians-University Munich (LMU). Up to that day, it was rated an inevitable, an absolutely essential condition, that donor and recipient have to have the same blood group in order to be able to transplant any organ. The Munich team was the first one to overcome this natural barrier.

Kidney transplantations: Biomarkers as a tool for prognosis

Perhaps it might be possible to determine whether an organ transplantation will be successful or not – some time in the future. Even today, US American physicians are in a position to find out by biomarkers whether a transplanted kidney will be fully functional or whether the patient will survive the surgery merely as a dialysis-candidate. In a study made on 53 patients with implanted kidneys, scientists of the Cincinnati Children's Hospital Medical Center found out, that high concentrations of the protein NGAL (neutrophil gelatinase-associated lipocalin) indicate a decelerated recovery of the kidney function and, from certain results on, might even indicate a partial failure of the organ. The biomarker IL-18 supplies valuable hints regarding a potential kidney failure after transplantation as well as proven in the Cincinnati studies. Their potential relevance in medical every day's life makes such findings so valuable. While today the determination of the creatinine to determine the kidney function is the tool, tomorrow physicians might be alerted by biomarkers such as IL-18 or NGAL – before the freshly implanted organ collapses.

The EU focuses on the triumph of transplantations

Questions like those do not only keep surgeons and biochemists busy, also politicians have understood their significance. Since September last year, professionals of the European commission are evaluating the results of a public hearing, set by the commission before, about future EU activities in the field of organ donation and -transplantation. Target of this hearing was “to find out the major problems in this context and to acquire, to what extent the EU should get active in order to solve those problems. In addition, one of the issues was to collect ideas to determine which initiatives the EU should take to decide on future EU politics in this field”. The interest of the politicians in Brussels seems appropriate. The death rate of patients waiting for a heart-, liver- or lung transplantation is at bout 15 to 30 percent – currently more than 40,000 patients are registered on waiting lists.

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