Adult stem cell application effective in treatment of peripheric vascular disease

January 24, 2008

Multipotent adult progenitor stem cells extracted from bone marrow, and known as MAPCs, have proved to be effective in the regeneration of blood vessel tissue and also in muscle tissue when treating peripheric vascular disease. This was the result of research undertaken with mouse models by two research groups, one by the University Hospital of Navarra jointly with the Centre for Applied Medical Research (CIMA), also of the University of Navarra, and the other by the Centre for Molecular and Vascular Biology atthe Catholic University of Leuven (Belgium).

The results of the study have been recently published as an article in The Journal of Clinical Investigation the main author of which is doctor in Biology at the University Hospital of the University of Navarra and CIMA, Xabier López Aranguren. The study was part of a line of research for his PhD thesis. The directors of the current research are doctors Felipe Prósper, for the University Hospital of Navarra and CIMA and Aernout Luttun and Catherine M. Verfaille for the Catholic University of Leuven.

Aim of research

Acute peripheric vascular disease involves the obstruction of the blood circulation in a determined area of the organism, as a consequence of the occlusion of the artery supplying blood to it, with the consequent reduction in blood flow. If it is not treated in time, the ischemia can cause various complications; the worst scenario being tissue necrosis, gangrene, or even the loss of an affected limb. In any case, the basic effect of peripheric ischemia is an important loss of vascularisation in the affected area, as well as in the musculature.

The research work published in The Journal of Clinical Investigation analysed the role and potential of two different types of cell-based treatments for peripheric vascular disease. It was based on the use of experimental mice models that were treated for this blood vessel ailment using MAPC cells implant and mononucleate cells from bone marrow.

MAPCs are multipotent adult progenitor stem cells obtained from bone marrow and which have a capacity for proliferating and differentiating in multiple tissues and which, thereby, comply with the criteria to be stem cells. The mononucleate cells from bone marrow are also a set of cells the hematies and plaques of which have been simply suppressed and, so, include stem cells but also differentiated cells such as monocytes and lymphocytes.

The study aimed to compare the efficacy of both cell populations in the treatment of peripheric ischemia given that the use of marrowbone cells for treatment of patients is currently being considered. Consequently, it is important to determine if there could be differences in the efficacy between the two types of cells.

The interest of the research lies in that the trunk cells analysed were not implanted in the same state as they were extracted. Also observed was the role that they might play when, before being transplanted, they are pre-differentiated into the concrete types of cell required. In this way, the idea was to see if greater benefit accrues from transplanting the cells just as they are extracted or if it is preferable to carry this out after differentiation has been achieved.

Results

The most important finding from the research was that adult MAPC stem cells are more effective when injected without pre-differentiation, not only because they contribute in increasing the quantity of arteries and veins generated in the new area, but also because they manage to enhance muscle regeneration. Although it is true that the muscle regenerates mainly thanks to an indirect phenomenon, not because the stem cells are differentiated in muscle cells, but because they help the muscle grow more and better as a consequence of secreting a series of substances. The research thus concluded that the MAPC progenitor cells implanted in mice achieved an indirect improvement of the muscle and a direct enhancement of the vessels.

On the other hand, the study also showed that, although the mononucleate cells are capable of regenerating in the short or medium term, the vascularisation of the mice damaged by the ischemia may have a negative effect in the long term. This is because transplanting mononucleate cells into the limbs of mice generate greater fibrosis with time. This conclusion has given rise to a certain degree of controversy as regards a number of current clinical studies that propose the use of mononucleate cells from bone marrow.

Human MAPCs and those of the mouse

The study was carried out on both cell populations from mice as well as humans. During the research the team from the University Hospital at the University of Navarra and CIMA was responsible for the experiments with human cells, while the University of Leuven team was in charge of the tests with mice cells.

Analysing the results from both models, the same degree of efficacy was observed, to such an extent that the experiments undertaken with MAPCs from mice and those from humans overlap, i.e. they both achieve identical benefits.
-end-


Elhuyar Fundazioa

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