Using versatile stem cells to fight leukaemia
Deutsche Krebshilfe supports new FAU research project
The Deutsche Krebshilfe (German Cancer Aid) is now providing approximately 630,000 euros in funding to a Max Eder Junior Research Group at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU). Dr. Dimitrios Mougiakakos (33) and his research group at the Department of Medicine 5 – Haematology and Oncology (head of department: Prof. Dr. Andreas Mackensen) at Universitätsklinikum Erlangen (Erlangen University Hospital) intend to use this funding to examine how mesenchymal stem cells function. It is their goal to prevent inflammation and rejection reactions in patients after bone marrow transplants using a new form of stem cell therapy.
Their hope for this new therapy are the multipotent mesenchymal stem cells (MSCs). They display numerous outstanding qualities with regard to tissue regeneration and the controlling of excessive immune responses. MSCs can be extracted from the bone marrow and subsequently proliferated with relatively little expense and difficulty. One of their special traits is their immunological ‘stealth’, meaning that the immune system does not detect and reject them. This means they may be safely transferred without taking into consideration blood and tissue types, which makes them an especially attractive method for modern cell therapy – and the method has already been used with promising success in cases of severe complications after bone marrow and stem cell transplants within clinical trials.
Especially for many types of leukaemic cancer, the destruction of cancer cells through chemotherapy or radiation followed by a bone marrow or stem cell transplant using the cells of a family member or other donor is the only kind of treatment promising a chance at recovery. The key to the success of such transplants is that the remaining cancer cells are detected and destroyed by the cells from the donor immune system. T lymphocytes, which are a type of white blood cell, are the main actors in this process. But in many cases the activated T lymphocytes of the donor immune system also react against the healthy cells of the recipient, resulting in graft-versus-host disease (GVHD). ‘This may affect almost all of the recipient’s organs. It frequently leads to painful skin alterations, diarrhoea and disturbances in liver function,’ explains Dr. Mougiakakos. Despite the significant progress made in the field of transplantation medicine, GVHD that does not respond to cortisone is very hard to keep in check. MSCs are becoming increasingly important in treating GVHD.
First studies show promising results
First clinical studies using MSC transfers to treat severe GVHD have shown promising results. The experimental data available so far suggests that the T lymphocytes act as agents for the positive effect of the MSCs. MSCs do not simply prevent the activation of T lymphocytes but rather adjust their responses: they create a balance between the different subgroups of T lymphocytes that inhibit inflammation processes (e.g. TReg cells) or promote them (e.g. TH17 cells).
The project funded by the Deutsche Krebshilfe is to focus on how MSCs control the T lymphocytes by interfering in their energy household. Current observations show that the metabolism of T lymphocytes is key to regulating immune responses. ‘We want to make use of the fact that the metabolism of activated T lymphocytes is in some ways similar to the metabolism of leukaemia cells, and transfer our insights onto the interaction of MSCs with leukaemia cells,’ says Dr. Dimitrios Mougiakakos. ‘This is important since a large percentage of GVHD patients have had a transplant because of leukaemia. Remaining leukaemia cells can potentially interact with the transferred MSCs.’ The resultant changes in the leukaemia cells’ energy production can be a significant influence on their aggressiveness and thus on the course of the disease.
‘With this promoted project, we intend to gain a better understanding of the biology of MSCs and thus to optimise MSC-based therapies,’ says Dr. Mougiakakos. At the same time, the insights gained by the researchers may be used for improved risk assessment before MSC therapies and may help in identifying new therapeutic goals with regard to the energy production of leukaemia cells. In future, this knowledge is expected to enable efficient and low-risk treatment of GVHD patients with MSCs.
Dr. Dimitrios Mougiakakos spent three years as a postdoctoral researcher on a DFG scholarship at the Karolinska Institute in Stockholm, Sweden. His work was particularly focused on the connection between metabolism and immune response, and he established a close working relationship with Prof. Katarina Leblanc, one of the pioneers in the clinical uses of MSCs. Since his return, Dr. Mougiakakos has led the research group ‘Translational tumour and transplant immunology’ at the Department of Medicine 5.
Dr. Dimitrios Mougiakakos
Phone: +49 (0)9131 85 43172