Improving the long-term health prospects of transplant patients has proved an elusive target so far. Although transplants are literally a life saver in the short term, research had not yet found a way to get round the risk of organ rejection, not to mention the need for immunosuppressive drugs which may cause a number of later problems in many patients, including cancers, infections, kidney problems, cardiovascular disease, diabetes and bone diseases.
But now, on the basis of the RISET ('Reprogramming the Immune System for the Establishment of Tolerance') and TRIE (Transplant Research Integration in Europe) project findings, new tests and techniques are being investigated that could reduce the number of immunosuppressive drugs transplant patients need to take.
Both projects have been funded by the European Commission. RISET’s partners have identified a molecular signature that is being turned into a test to predict which patients could safely reduce their intake of immunosuppressive drugs. This would depend on the expression of certain genes in the blood. Researchers are convinced that in the case of liver transplants, as many as 20% of transplant patients could survive without many of these immunosuppressive drugs. It means that too many patients are, in fact, over-immunosuppressed.
The RISET team has also found that the immune system's tolerance of the donated organ can be improved if so-called 'tolerogenic' cells are transplanted along with the organ. These tolerogenic cells effectively “educate” the host's immune system to accept the new organ, and would quite possibly reduce the need for immunosuppressive treatment. Basically, evidence is adding up that tolerance to organ transplants can be induced, and that it will require the infusion of donor cells endowed with such tolerogenic properties. These may be hematopoietic stem cells or other type of myeloid cells derived from the blood.
“We hope the use of tolerogenic cells and biomarkers can be used to tailor treatment to patients all over the world and we have a number of data proving this is indeed the future”, Professor Michel Goldman, the project’s coordinator, said. “Hopefully, this should make transplants more successful and safer in the long term”.
RISET is the research project; TRIE contains, among other things, a patient survey and the recommendations to the European Commission about a common European approach for transplantation research bringing together academia, clinicians, industry and patient organizations. Such recommendations focus on three priorities. TRIE’ first goal is the development of biomarkers in donors and recipients, in order to define risk profiles and tailor pre- and post implant therapies. The second regards the development of novel cell-based therapies. The third calls for innovative training programmes for transplant surgeons, scientists and healthcare staff.
These recommendations have already struck a major chord within the transplant community. In fact the most widely held view is, if solid organ or cell rejection could be predicted and tolerance induced, it would be a sea change indeed.
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