Stem cells are multipotent cells of the immune system. Scientists hope to use them for curing autoimmune diseases, cancer and innate genetic defects in the future. What is possible today, which barriers still need to be overcome and how research in this area is progressing - these were topics of the lecture held by Professor Fritz Melchers, a doyen of immunology and Honorary President of the 2nd European Congress of Immunology in Berlin at a Press Conference.
For decades now, experimental and clinical immunology has been using cell transplants for multiplying and restoring the hematopoietic (blood-forming) system of our body, i.e., of red blood cells and cells of the innate and the adaptive immune system. A clinically successful cell therapy which is performed more than 30,000 times a year is bone marrow transplantation. It is particularly widely applied in cancer patients for life-long restoration of the deathly damaged hematopoietic system after chemotherapy or radiotherapy.
Severely immunodeficient children also receive bone marrow transplants to repair their defective system using bone marrow cells of a suitable healthy donor. This is possible because the bone marrow contains small amounts of what are called hematopoietic stem cells. It has been shown experimentally that, in principle, a single stem cell is capable of restoring the whole system of over 2000 billion blood and immune cells.
A serious problem of such transplantations continues to be what is called tissue incompatibility. This means that the recipient's (patient's) immune system - even in the deficient state that is sometimes left in cancer patients and immunodeficient children - rejects and destroys the cells of the donor, i.e., the stem cells and the blood and immune cells derived from them. In the reverse case, it can also happen that the donor cells attack the patient's organism. In clinical transplantation practice, these rejections are suppressed by chemical substances, i.e., immunosuppressive drugs that have to be taken life-long after transplantation. Immunosuppressants naturally weaken the defense of the newly restored immune system against infections and affect the control of autoimmune (directed against the own body) reactions of the system.
"Thus, we are searching for tissue-compatible forms of transplantation. It would be best if the cancer patient could receive his or her own healthy stem cells, because they would be tolerated and not rejected," says Melchers. "However, since the bone marrow of cancer patients is 'contaminated' by cancer cells, transplantation of 'own' bone marrow is out of the question."
In severely immunodeficient children, the stem cells are defective, too. In the past, Professor Alain Fischer of the Hôpital Necker in Paris tried to correct the deficient stem cells of these children by repairing the defective gene and subsequently returning the gene-therapeutically repaired stem cells to the immunodeficient children. This was successful in approximately ten cases. However, some of the transplanted children developed blood tumors as a result of the mutagenic effect of the retroviral gene delivery vehicle. Retroviruses are used as "gene ferries" to insert the repaired gene into the genome of the stem cells. Although the tumors could be cured, the severe immunodeficiency remained.