Monday, January 28, 2008

[StemCells] MAPCs for PAD

Adult stem cell application effective in treatment of peripheric
vascular disease
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.

Public release date: 24-Jan-2008

Contact: Egoitz Etxebeste
egoitz@elhuyar.com
Elhuyar Fundazioa

http://www.eurekalert.org/pub_releases/2008-01/ef-asc012408.php

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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