What Works Better: Stem Cell Mobilization or Stem Cell Administration for Brain Injury

Bakhtiary et al. Iran Biomed J. 2010 Oct;14(4):142-9.

Bone marrow mobilization is used as part of hematopoietic stem cell transplantation in order to collect donor bone marrow stem cells without having to puncture the bone. The process of mobilization is induced by administration of the drug G-CSF, which is approved by the FDA. One interesting question is if instead of giving patients stem cell therapy, if one could simply give G-CSF and have their own stem cells “mobilize” and treated the area of injury. This would be simple and economical as compared to injection of stem cells.

In order to test this, a group from Iran used a rat model of traumatic brain injury and gave either G-CSF or bone marrow derived mesenchymal stem cells.

There were three groups of 10 rats used in the experiments. All rats were subjected to traumatic brain injury by use of a “controlled cortical impact device”. The first group received 2 million bone marrow derived mesenchymal stem cells. The second group received G-CSF to mobilize the bone marrow stem cells. The third group served as a control group. All injections were performed 1 day after injury into the tail veins of rats. The bone marrow derived mesenchymal stem cells were labeled with Brdu before injection into the tail veins of rats. Animals were sacrificed 42 days after TBI and brain sections were stained by Brdu immunohistochemistry.

As compared to controls, both the G-CSF mobilized and the bone marrow mesenchymal stem cell groups had a statistically significant improvement in behavior. When animals were sacrificed at 42 days the observation was made that labeled bone marrow mesenchymal stem cells homed into the area of injury and appeared to contribute to repair.

Although more date is needed when it comes to clinical application, it may be feasible to use G-CSF as part of therapy for traumatic brain injury. One caveat that we find with this is that G-CSF, as its name suggests (granulocyte colony stimulating factor), actually stimulates both increase in granulocyte number and function. While in a controlled laboratory environment brain damage may be relatively “sterile”, in the clinical setting it may be that increased granulocytes may contribute to a higher extent of inflammation and therefore more tissue damage. On the other hand it is possible that mesenchymal stem cells because of their known anti-inflammatory activity may function not only to regenerate the injured brain tissue but also to provide an anti-inflammatory effect.

Hope for Brain Injury Victims

Traumatic brain injury (TBI) is a major health problem
caused by a sudden trauma to one or more areas of the brain. Today the
conventional method of treating patients with TBI is based on administration of
supplements to rebalance the brain’s chemistry. In the early phases of TBI
reduction of the ongoing inflammation using various antioxidants and
anti-inflammatory compounds has demonstrated some promise. Unfortunately, after
the injury has occurred there is little that can be done with the exception of
physiotherapy programs to allow the patient to cope with loss of function.

Although the traditional belief has been that once the
brain is damaged, regeneration is non-existent, recent findings suggest that
this may not be entirely true. Specific parts of the brain (subventricular
zone) have been demonstrated to contain stem cells that begin to multiply and
make new brain cells (neurons) after injury. Although this healing process is
often not potent enough to cause a robust effect that can be seen clinically,
the fact that it exists pushes scientists to find ways of amplifying it.

It was discovered more than twenty years ago that pregnant
pigs have areas of the brain in which cells multiply. The more recent finding
of brain stem cells has prompted researchers to ask whether administration of
pregnancy-related hormones can actually accelerate healing of injury brains.
Scientists at the Canadian company Stem Cell Therapeutics have shown that
administration of the hormone human chorionic gonadotrophin (the same hormone
detected by the pregnancy test) to animals with TBI can accelerate recovery. We
have previously discussed here that this company is now in clinical trials with
this approach for stroke, another type of brain injury
www.cellmedicine.com/stem-cell-therapeutics-placement.asp.

Another approach to treating TBI involves administration of
stem cells from outside of the body. This approach has previously been used for
conditions like heart failure

http://www.youtube.com/watch?v=flv0RmzPyLU
, liver failure

http://www.youtube.com/watch?v=DdH6Mm4w98I
, or multiple sclerosis

http://www.youtube.com/watch?v=wIcUaKZWOSE
.

Recent studies have demonstrated that animals in which TBI
was induced, the administration of bone marrow stem cells results in
regeneration of damaged areas. It is currently unclear whether the stem cells
themselves are becoming new neurons, or whether the stem cells are producing an
environment in which the existing brain stem cells may exert their activity.
The University of Texas has recently completed a 10 patient clinical trial of
children with TBI treated with their own stem cells

http://www.clinicaltrials.gov/ct2/results?term=NCT00254722
, however the
results have not been published yet.

One example of the potential of adult stem cells in
treatment of brain damage is illustrated in a scientific report from Russia in
which comatose patients where treated with stem cells and consciousness was
regained (Seledstove et al. Cell therapy of comatose states. Bull Exp Biol
Med. 2006 Jul;142(1):129-32
).

The potential of stem cell therapy for TBI is anticipated
to be promising. Dr. Paul Breen, a specialist in TBI stated ""This new research
in stem cell research is a huge breakthrough and highly anticipated. We hope
that this could help pave the way for future research in stem cell usage for
brain trauma treatment in the coming years. If it works, it could give thousands
of people who have suffered brain injury hope of, if not a complete recovery,
then certainly a much better quality of life and a restoration of many of their
physical and mental functions. It’s a strong case in favour of continued stem
cell research."