Projects / Programmes
Use of mesenchymal stem cells to target gliomas: Risk assessment and evaluation of umbilical cord blood-derived mesenchymal stem cells as new cellular vectors for therapy.
| Code |
Science |
Field |
Subfield |
| 1.03.00 |
Natural sciences and mathematics |
Biology |
|
| Code |
Science |
Field |
| B210 |
Biomedical sciences |
Histology, cytochemistry, histochemistry, tissue culture |
Umbilical cord blood, mesenchymal stem cells, glioblastoma, brain tumour stem cells
Researchers (8)
Organisations (2)
Abstract
Glioma is the most common cancer of the central nervous system and patients with glioblastoma, its most malignant form, have a life expectancy of under a year. One of the main reasons for treatment failure is the highly infiltrative nature of these tumours, which impedes their complete removal by surgical procedures. This is coupled to an inability to specifically deliver available therapeutic agents to all the invading tumour cells. Studies on neural and mesenchymal stem cells have demonstrated a natural tropism of these cells towards glioma tumours. Very importantly, they also track the tumour cells that invade through the normal brain parenchyma, which could make them ideal vectors for the efficient and more selective delivery of anti-cancer agents. In addition to the ethical issues raised by the isolation of human embryonic neural stem cells, there are also some important shortcomings to the use of mesenchymal stem cells (MSC) obtained from bone marrow. There is evidence suggesting that some of these problems might be circumvented by using MSC derived from other tissues such as umbilical cord blood. One of the main aims of this project is to assess, for the first time, the potential of these cells as possible vectors for anti-glioblastoma therapies. In parallel to this work, the project also addresses what is now becoming a very serious concern, the possible contribution of MSC towards tumour progression. Their effect on the proliferation and invasive abilities of glioblastoma cells will be assessed, as well as two other aspects thus far ignored, the effect of MSC on the response of glioblastoma cells to cell death-inducing agents, and their possible interaction with the so-called brain tumour stem cells. These latter have been associated to higher tumour malignancy and put forward as key players in the resistance of gliomas to anti-cancer therapies and the recurrences that inevitably lead to the death of glioblastoma patients. These are all key questions that will need to be answered before really contemplating the use of MSC in the clinical setting.
Significance for science
When the project was originally proposed it presented the first steps in characterisation of mesenchymal stem cells (MSC) acquired from cord blood/cord, to be used as potential vectors in therapies of cancer. At the time, there were no scientific publications covering that field yet and our proposal presented a completely new idea. Further, there was very little known about the influence of MSC from the umbilical cord on gliomas. During the duration of this project however, several papers were published in the field confirming the actuality and significance of the subject. In the last few years the number of publications is constantly increasing, testifying that the theme of this project followed the lines of most actual and advanced research in the field of isolation and function of MSC.
We did not manage to establish a stable culture of MSC from umbilical cord blood, possibly due to the low number of these cells in the blood itself. In our opinion, this is an important result worth publishing, as the expectations concerning preservation of umbilical cord blood might be too high.
During our project we confirmed that umbilical cord presents an important alternative source to bone marrow in mesenchymal stem cells isolation. Further, we did not observe MSC's transformation that would stimulate the harming activity of glioma cells and render the potential use of MSC in cancer therapy impossible.
The key question of our project, if the mesenchymal stem cells could be applied as vectors in glioblastoma, extremely rarely curable type of cancer, is partially answered. The results of our research have shown that MSC hindered the glioblastoma cells by inhibiting their proliferation and invasion and stimulate their senescence. Identification of cytokines involved in interaction between MSC and glioblastoma cells indicated several new cytokines that were not previously considered to affect the tumour cells invasion. That opens a full new range of questions on the function of MSC and presents a firm basis for further research in application of MSC in therapy of gliomas.
Significance for the country
The research in the field of mesenchymal stem cells represents a new direction in cell biology as well as in new treatments development and in regenerative medicine. The main aim of the current project was to identify the potential value of MSC acquired from umbilical cord blood/ umbilical cord in treatment of gliomas. Therefore, it was of vital importance to identify the alternative source, which would enable us to isolate MSC of high quality and in sufficient number. As the Slovene bank of bone marrow donors has very limited capacities, the isolation, characterisation and culturing of MSC from umbilical cord is very important for Slovenia in potential treatment of some types of cancer. There are several umbilical cord blood preservation banks in Slovenia, from Slovenian as well as from foreign enterprises, for which the information on the use of the cells from this source is very important, as the donors should be aware of the limits of their biological material for treatment.
The clinical application of stem cells requires a high expert knowledge support and sufficient technological equipment. Therefore a Slovenian Stem Cells Centre was established in 2009, joining 11 scientific and commercial partners, including our Institute and Educell company.
Despite the results of our project, many questions remain unanswered. Only these answers would enable the final confirmation of the suitability of MSC for cancer treatment. Following the results of this project, we hope to continue the study of interactions between MSC and glioblastoma in the new form.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
