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Skop’s ultimate
goal is to use his
scaffolds and fetal
stem cell line to
regenerate the
injured brain at
the site of a severe
injury.
4 2 U M D N J M A G A Z I N E
Europe — calling
themselves the
Transatlantic Network
on Newborn Stroke —
who received a $6 million
grant from the
Paris-based Fondation
Leducq to investigate
their premise that newborn
brain injury may
be reparable. His
dream is to impact clinical
practice with his
lab’s findings within
just a few years.
Levison’s lab has
demonstrated that brain injury in the infant stimulates the proliferation
of stem cells within the “brain marrow,” resulting in a doubling
of their number after just three days, and that the new stem
cells can generate new neurons and glia. What they are battling is a
highly destructive cascade of inflammatory molecules that is set off
at the time of trauma.
Levison is also the principal investigator on a sizable grant
from the New Jersey Commission on Brain Injury Research,
which underwrites three collaborative projects at UMDNJ and
NJIT to devise strategies to enhance regeneration of brain cells
and to promote recovery of function after traumatic brain injuries
(TBI). Cho and Gandhi work with him on these projects.
In May 2009, Skop began his research work on neural stem
cells in Gandhi’s NJMS lab. His undergraduate degree had concentrated
primarily on civil and electrical engineering, so the doctoral
student now focused on bolstering his knowledge of biology,
specifically neurobiology, in order to delve headlong into medical
research. “I took all four of the graduate stem cell classes offered
plus a regenerative medicine class,” he says. Skop earned a certificate
in stem cell biology in 2010 and also took on the presidency
of the Stem Cell Education Society at UMDNJ.
In Gandhi’s lab, he learned how to harvest stem cells from
the subventricular zone of a healthy animal and transplant them
adjacent to the damaged cerebral cortex of another that is braininjured.
The transplanted cells — glowing a fluorescent green —
are easily distinguishable from the native cells.
Skop has worked with both fetal neural stem cells and adult
neural stem cells. “We transplanted both kinds after a fairly
severe brain injury to see which would give the best results,” he
says. “We were looking to see what the stem cells differentiated
into and the numbers of transplanted cells that survived.”
Unfortunately, “very few of the cells survived the transplant,”
he states, “which is in line with other research out there.”
But since science is all about asking the right questions,
Skop took the next step and worked on framing the pivotal question
for his research project. Could new engineering techniques
— some of which he had recently learned in Cho’s biomedical
engineering lab — be applied to improve the model and consequently
the outcomes?
One answer was obvious: He needed to abandon working on
the adult stem cells because of their serious limitations and
concentrate on the fetal stem cells, which were showing far more
promise for regeneration. The second answer was less obvious
and would demand further investigation: The stem cells needed
to be placed differently in the cavity formed from the brain
injury. “I started injecting the cells into the tissue surrounding
the cavity but they weren’t migrating into the injured tissue to
replace the damaged neurons,” the student explains.
Skop was on the right track, but not quite there. Tissue
engineering is all about applying engineering principles, as well
as knowledge and skills in the life sciences, to develop new
strategies to repair, and new materials and structures to replace,
tissues and even whole organs that are no longer functional or
viable. Stem cells, novel biomaterials, and growth factors are used
hand-in-hand with bioengineered structures — such as scaffolds
— to support the growth of new tissue.
Now the graduate student decided he was ready to move
forward with his doctoral project, using his engineering background
to create a unique scaffold to promote the regeneration of
brain tissue. “My first step was to optimize my scaffold, which
turned out to be a lot of work. I’m still trying to improve it,” he
explains.
His idea was that the scaffold would be multifunctional,
serving as a delivery vehicle to get the stem cells to the right
place, to provide a “hospitable” surface for the stem cells to grow
on, and, by attaching a growth factor to the scaffold, a means to
enhance the growth and survival of the newly introduced cells.
The scaffold that Skop created in the NJIT lab—made of
microspheres of chitosan — is still being tested, but is “95 percent
complete,” he says with a smile. One of his major hurdles
was to radically reduce the size of the microspheres in order to
facilitate transplantation into the brain of the animal model. With
his engineering skills and ingenuity, he accomplished his goal.
He physically carries his mini scaffolds — small enough to fit
in the palm of his hand — on the CHEN bus linking the campuses
of Newark’s major universities. They are “engineered” at
NJIT but it is in the UMDNJ lab that he has tested them with a
fetal rat stem cell line. “It works!” he says proudly.
Skop’s ultimate goal is to use his scaffolds and fetal stem cell
line to regenerate functional brain tissue at the site of a severe
injury. “I want my work to be clinically relevant,” he states.
“We produce a cavity-type of brain injury, which causes cell
death under the injured site. This area would normally scar, but
the scaffold also provides a physical and chemical barrier to the
scarring process,” he explains.
Skop sees this as the beginning of a “huge, very ambitious
research project,” in which he will show that the stem cells can
be transplanted at the site of the injury, survive, proliferate and
regenerate dead neurons. He hopes that in one year he will have
some significant results to show.
Rebuilding an injured region of the brain is among the most
complex undertakings in the world of medical research. “The
brain and nervous system are difficult. People are afraid of this
field,” says Skop, “If we are successful, our work will send ripples
throughout the whole regenerative medicine community.”
And that is just a glimpse of what one doctoral student with
three supportive research mentors in two distinct specialties can
accomplish when they put their heads together. .