Tissue regeneration operates differently than expected

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Tissue regeneration operates differently than expected

05 Aug 2005

http://www.medicalnewstoday.com/medicalnews.php?newsid=28645

Max Planck researchers in Bad Nauheim discover the mechanism by which

adult stem cells are integrated into skeletal or heart muscle tissue.

There is disagreement, however, about the mechanism on which repair

processes are based. Scientists from the Max Planck Institute for

Heart and Lung Research in Bad Nauheim, Germany, in co-operation with

colleagues from Luther University in Halle-Wittenberg, have

now shown that skeletal muscle tissue can fuse with adult stem cells,

via a mechanism based on the participation of mediators which are

generally involved in immune cell activation. Although being unable

to transdifferentiate into completely functional muscle cells, they

are integrated into the tissue complex by fusing with differentiated

tissue cells. In contrast, in the heart muscle tissue the mechanism

seems to be different from this. The scientists in Bad Nauheim

conclude from their study that adult stem cells are involved in

tissue repair processes in a paracrine way by delivering mediating

factors rather than by simply becoming components of the regenerating

organ. (Genes & Development, August 2005).

Stem cells are fully unspecialised cells which can develop into all

kinds of cell types. Embryonic stem cells provide the origin of a

developing organ, during the growth of an embryo. For example,

mesenchymal cells - stem cells from embryonic connective tissue -

transform themselves during embryogenesis into muscle cells, under

the influence of certain growth factors.

Other stem cells - adult stem cells - play an important role

throughout an organism's life. For example, bone marrow stem cells

provide for the replenishment of short-lived blood cells. Adult stem

cells can be found locally in various tissues and organs, and we have

presumed that they are participating in the repair and maintenance of

organ functions.

The controversial idea is that adult stem cells have the potential

for transdifferentiation; in other words, that they are able to

transmutate from one type of organ cell to another. If that is the

case, bone marrow cells would be able to change into lots of

different kinds of tissue cells - for example, skeletal muscle cells.

Scientists led by Braun, Director of the Max Planck Institute

for Heart and Lung Research, have discovered by a number of different

experimental approaches that mesenchymal stem cells only show a

rudimentarily developed potential for transdifferentiation processes.

All cases in which functional skeletal muscle cells arose from

mesenchymal stem cells were based on the fusion of stem cells with

already differentiated muscle cells.

Although, like the researchers from Bad Nauheim show, cultivated

mesenchymal stem cells are able to express a number of heart- and

skeletal muscle specific genes and undergo some morphologic changes,

after they are co-cultured with growth-factor producing feeder cells,

finally they did not become entirely functional muscle cells.

Fully-functional muscle cells only developed after the mesenchymal

stem cells were cultivated together with skeletal or heart muscle

cells. This was indicated by the green fluorescence of muscle cells

derived from the fusion with a stem cell which before had been

labelled with the green dye. In contrast, no green fluorescing muscle

cells became evident when stem and muscle cells were spatially

separated by a membrane between both cell types. The researchers

conclude that this experiments proofs that cell fusion of mesenchymal

stem cells and muscle cell but not their transdifferentiation forms

the basis for the regeneration mechanism. Additional experiments were

focussing on the molecular mechanism underlying the cell fusion

process. In these investigations, so-called " chimeric " mouse embryos

were produced from mesenchymal stem cells and several mouse mutants:

Obviously, the stem cells are recruiting the IL-4/NFAT signalling

pathway which also is involved in the activation of T-lymphocytes

during immune response.

From the findings presented by Braun and his collaborators

some important consequences for the use of adult stem cells in

possible therapeutic approaches could arise, since they contradict

the predominant opinion that bone marrow-derived or local stem cells

are involved in the regeneration of heart and skeletal musculature by

transdifferentiating into muscle cells. By fusing with the cells of

the regenerating tissue these cells rather seem to only simulate such

a transdifferentiation mechanism. This has major implications for the

prospects of stem cell therapies targeting on the regeneration of

skeletal or heart musculature.

Prof. Dr. Braun

49-6032-705-402

Max-Planck-Gesellschaft

http://www.mpg.de