Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Transplants - are mice leading the way?

05.07.2004


A new protocol for bone marrow transplants, which does not require the destruction of the recipient’s immune system before transfer of the new bone marrow, is described by a group of Oxford scientists in the 6th of July issue of the Proceedings of the National Academy of Sciences of the United States of America.

Furthermore, Luis Graça, Alain Le Moine, Herman Waldmann and colleagues from the University of Oxford, UK also found that following bone marrow transplant it is possible to successfully transplant other organs from the same donor, including skin, the most difficult organ to be successfully transplanted, into this now hybrid/chimeric bone marrow recipient.

The number of human tissue transplants is on the increase all over the world. In Europe, hundreds of thousands of tissue transplants are performed each year, while only in 1999 as many as 750 000 people in the United States of America received human tissue, twice as many as in 1990.



Graça, Le Moine and Waldmann’s team have been working with mice for a number of years to find alternative protocols for safer and more effective organ transplantations.

Because the immune system has evolved to react against any foreign intruder while remaining non-responsive against its own body, organs from other individuals are seen as foreign and so potentially dangerous which leads to their rapid destruction by the immune system, the body’s defence mechanism. This creates serious problems in clinical transplantation and until now only the use of strong immunosuppressive drugs permits relative transplantation success. This however is not ideal, not only because rejection frequently occurs but also because these drugs compromise the entire immune system making individuals much more susceptible to infection or cancer.

Graça, Le Moine and colleagues work on an alternative model of tolerance based on the use of antibodies against several proteins found in the cells involved in organ rejection. Although the idea of antibodies is not new, these have been mostly used to delete entire populations of cells involved in the graft rejection process. This has the disadvantage of creating “ holes” in the immune system and, like the immunosuppressive therapies widely used in transplant, increase the recipient/host’s disease susceptibility.

What is interesting about the Oxford’s scientists work is that their antibodies do not seem to kill the host cells involved in organ rejection but instead apparently re-programme these cells rendering them tolerant to the foreign organ while leaving the remaining immune system intact and fully operational. It is this specificity of the treatment, the capacity of only making tolerant the cells specific for the foreign organ while keeping the remaining immune system undamaged, that makes Graça, Le Moine and colleagues’ work so exciting.

However, it is still not clear what the mechanism is behind this organ-specific tolerance and this has created problems to the development of human therapies. In the work now published, Graça, Le Moine and colleagues investigate claims that CD4+CD25+ TCR+ cells, a group of cells of the immune system called this way because they express in their cellular membrane the three proteins: CD4, CD25 and TCR, are capable of regulating specific parts of the immune system without affecting the remaining immune cells and might be the cells responsible for inducing the type of organ transplant tolerance observed after Graça and Le Moine’s antibody therapy.

Unfortunately, the results by the team of scientists do not support the hypothesis. Nevertheless, this is still a very important result as it undoubtedly challenges the wide spread assumption that these cells are main regulators of immune responses.

Furthermore, Graça, Le Moine and colleagues also describe a new protocol for bone marrow transplantation and successfully achieve a skin graft transplant between totally different donors and recipients something never achieved before without immune deletion.

In fact, the team of scientists show how a course of their non-depleting antibodies, which are specific for proteins found on the membrane of the cells involved in graft rejection, when given at the same time as a bone marrow transplant, leads to complete acceptance of this foreign bone marrow. This is extraordinarily important as the normal protocol for bone marrow transplants require at least partial destruction of the recipient immune system so the new bone marrow would not be rejected.

Graça, Le Moine and colleagues also show for the first time that skin from a fully foreign donor is also accepted if this organ is transplanted together with bone marrow cells from the same donor while receiving the team’s set of tolerogenic antibodies.

These results are extremely important first because they describe an alternative and much more effective protocol to control the immune system in bone marrow transplants. Secondly, their new protocol of transferring bone marrow together with the organ to transplant proved much more effective, to such a extent that even a totally foreign skin graft was successful, something which has never been accomplished before in the absence of immunosuppression. In a world where more and more transplants are necessary as result of an increasing aging population this is a critical breakthrough.

Finally, Graça, Moine and colleagues capacity of “ re-programme” the immune system without affecting its whole capacity to fight infection might prove extremely important also in other diseases where pathology results from deregulation of the immune system as it seems to be the case in diabetes, rheumatoid arthritis or multiple sclerosis.

Ana Paula Gravito | alfa
Further information:
http://www.oct.mct.pt

More articles from Life Sciences:

nachricht Polymers Based on Boron?
18.01.2018 | Julius-Maximilians-Universität Würzburg

nachricht Bioengineered soft microfibers improve T-cell production
18.01.2018 | Columbia University School of Engineering and Applied Science

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Polymers Based on Boron?

18.01.2018 | Life Sciences

Bioengineered soft microfibers improve T-cell production

18.01.2018 | Life Sciences

World’s oldest known oxygen oasis discovered

18.01.2018 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>