Fat May Serve a Purpose in Stem Cell Research

Scientist Dr. Joseph Wu at the Stanford University School
of Medicine has recently published a new and improved method to generate stem
cells "artificially".  For almost a decade there has been substantial
controversy regarding the use of embryonic stem cells, with the debate becoming
socially and politically focused as opposed to based on science: one camp
believing that embryonic stem cell research must be supported at all costs, the
other camp believing that adult stem cells can do anything that embryonic stem
cells can do, so there should be no research performed in this area.  This
debate became somewhat irrelevant when the Japanese group of Yamanaka discovered
a method of "dedifferentiating" adult cells into cells that appear at a
molecular and functional level similar to embryonic stem cells.  These
"artificial" stem cells, called inducible pluripotent stem cells (iPS) have
several unique properties:  They don’t need to be extracted from embryos; they
can be made from the same patient that they will be used on; and the methods of
manufacturing can be relatively standardized. 

To date these cells have been demonstrated to be capable of
generating not only every tissue in the body tested, but they also can improve
disease conditions in animal models ranging from heart attacks, to liver
failure, to bone marrow reconstitution.  Unfortunately the biggest problem with
iPS cells is that they are difficult to generate.  In order to understand this,
it is important to first mention how the cells are made.  Adult cells have the
same DNA blueprint as embryonic stem cells.  However in adult cells certain
portions of the DNA are not used to make proteins.  So in liver cells the DNA
that encodes for proteins found in the skin is "silenced" or "blocked" from
making proteins by various chemical modifications that occur as a cell is
maturing.  Embryonic stem cells are considered "blank slate" cells because the
DNA is capable of expressing every protein found in the body.  In order to make
an adult stem cell "younger" so as to resemble an embryonic stem cell, it is
necessary to somehow reprogram the DNA in order to allow it to express every
gene.  So how would one go about doing this? There is one biological condition
in which adult cells take the phenotype of younger cells.  This is in cancer. 
This is the reason why some types of cancer start expressing proteins that other
cells normally produce.  For example certain liver cancers can produce insulin,
even though liver cells do not produce insulin.  The concept that certain cancer
genes can evoke a "rejuvenation" of adult cells was used by Yamanaka as a
starting point.  His group found that if you insert the oncogene c-myc, together
with the stem cell genes Nanog, Oct-4, and SOX-2 skin cells will start to look
like embryonic stem cells.  If these cells are placed on top of feeder cells
then they can be expanded and used as a substitute for embryonic stem cells.

The current problem with wide-scale use of this approach is
that insertion of the various genes into the cells requires the use of viruses
that literally infect the cells with the foreign genes.  Not only can the
viruses cause cancer, but also the genes administered can cause cancer because
they are oncogenes.  The other hurdle is that generation of iPS cells is a very
inefficient process.  It takes approximately 2-3 months to generate stable
cells, and these cells are usually generated from approximately 1 out of
100-300,000 starting cells.  We previously discussed advances that allowed for
uses of non-hazardous means of inserting genes into cells to make iPS

http://www.cellmedicine.com/thomson-safer-ips.asp
, in this current article
another approach was described to increase efficacy.

Scientists used as starting population not skin cells,
which are considered substantially differentiated, but instead used fat derived
stem cells.  This type of stem cell is very much a mesenchymal stem cell

http://www.youtube.com/watch?v=qJN2RyBj78I
and possesses ability to
transform into different tissues already.  Thus by starting with a cell that is
already more "immature", scientists have been able to increase the rate of iPS
generation, as well as, alleviate the need for the oncogene c-myc.

Other approaches being investigated on increasing
generation of iPS cells include use of chemicals that affect the DNA structure
such as valproic acid.  This is interesting because simple administration of
valproic acid on bone marrow stem cells has been demonstrated to increase their
"stemness"

http://www.youtube.com/watch?v=3Hc4LCUOSiA
.

Although we are still far from the day when
individual-specific stem cells will be available for widespread use, we are
getting closer to this dream at a very fast pace.

2010-02-26T19:32:09+00:00February 26th, 2010|Adult Stem Cells, Embryonic Stem Cells, News, Stem Cell Research|