University of California Irvine Stem Cell Research

The University of California is fully for embryonic stem cell research. The first
embryonic therapy was held by them
o They believe in this because of the many helpful uses

They believe that it is completely acceptable to do Adult stem cell research

o For the many helpful causes
The uses of stem cells include
o Curing Paralysis
o Curing multiple sclerosis
o Curing ALS
o Teat other harmful injuries and diseases

http://research.universityofcalifornia.edu/stories/2011/10/stem-cells.html
The ultimate goal of human stem cell research has always been to harness the potential power of
these cells to treat and cure intractable diseases.
By transplanting millions of healthy stem cells into patients with a specific defect be it paralysis,
multiple sclerosis, ALS or others that are crippling and devastating clinicians expect these
pluripotent cells to develop into normal mature cells and take over critical functions of damaged tissue.
An accelerating research pace has prepared the way for the first stages of clinical trials, and UC
scientists have paved the way to some of the first tests of stem cell therapies.
In 2009, a treatment developed by UC Irvine neuroscientist Hans Keirstead became the worlds first
human embryonic stem cell therapy approved by the FDA for early-stage clinical trials. The treatment,
now being carried out by Geron Corp., is designed to lessen the impact of severe spinal cord injuries
by replacing lost myelin, the substance that normally insulates nerve cells and promotes
communication between them.
In preliminary research with embryonic stem cells, the scientists were able to derive cells that could
develop into healthy myelin-producing cells. Injected into animals, these cells went on to produce
functioning myelin, allowing electrical conduction to resume in the nerves and enabling injured animals
to walk again.
With this aim, three patients with severe spinal cord damage have been injected with human
embryonic stem cells. If successful, the procedure will restore the communication between neurons,
and thereby restore their ability to walk and move normally.
The early human trials test the safety of the procedure. The patient treatments began in October 2010.
No adverse signs have been reported.
Things are looking good, Kierstead reports.

Treating a severe childhood disorder

Defective myelination of nerves also is observed in multiple sclerosis, cerebral palsy and a rare and
fatal brain disorder called Pelizaeus-Merzbacher disease (PMD). This disorder is caused by a
defective gene on the X chromosome that boys inherit from their mothers. Children affected with the
severe form of PMD cant walk or talk, and often die between ages 5 and 7.
Clinical trials were approved in 2009 for a stem cell therapy to treat PMD. This trial uses adult rather
than embryonic stem cells. Both types have the remarkable ability to develop into many different cell
types in the body. While embryonic stem cells are thought to be capable of specializing into any type of
cell, adult stem cells are more limited mainly able to differentiate into cell types from the tissue they
are drawn from. But because of their more focused specialization, they may be less likely to be
rejected after transplantation.
This (PMD) is a tragic disease, and I think the families are aware that these early trials may not help
their children, said UCSF physician-scientist David Rowitch (in photo above). But they recognize that
it might help other children, and theyre very dedicated. Im so impressed by how involved and
engaged the families are in supporting the trials.
These early clinical trials are aimed at determining the safety of the stem cells being tested, a critical
first step toward developing any effective therapy, said Arnold Kriegstein, director of the Eli and
Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.
In PMD, as in spinal cord injury, specialized cells called oligodendrocytes fail to make myelin. Rowitch
and colleagues are collaborating with StemCells, Inc. in a clinical trial, testing the safety of injecting
PMD patients with adult neural stem cells that can lead to healthy oligodendrocytes. They hope normal
oligodendrocytes might be able to provide the needed myelin. Results of the clinical trial will be
assessed in 2012.
We are not trying to kill off the defective cells, but to restore the brains ability to produce a supply of
normal myelin by providing healthy oligodendrocyte precursors, said Rowitch, principal investigator on
the trial and a pediatric specialist and chief of neonatology at UCSF Childrens Hospital. Rowitch also
is a Howard Hughes Medical Institute Investigator in UCSF's Broad Center. These cells have the
capacity to identify areas of the brain lacking myelin, so if they can survive after transplantation they
may be able to form myelin in the brain of PMD patients.
In the study, UCSF neurosurgeon and co-principal investigator in the trial Nalin Gupta transplanted
adult neural stem cells directly into the brain of four patients.
Critical to monitoring the treatments progress, the trial calls for patients to receive MRI scans of their
brains before the treatment and then every three months for a year to assure that the new cells do not
cause widespread brain inflammation or other problems.
In addition, neurologist Jonathan Strober, also co-principal investigator, monitors the patients
symptoms to identify any signs of clinical improvement or deterioration.
If the trial shows evidence of safety and of myelin production, it could point the way to a whole new
approach to treating of PMD and other childhood brain disorders, said Rowitch says.

We still have much to learn about human stem cells therapies, but I hope we can look back on this
time as the very beginning of a wave of treatments for intractable diseases, said UCSFs Kriegstein.
'Borrowing' a patients stem cells
In both the UC Irvine and UCSF clinical trials, a specific type of normal donor stem cell is introduced to
patients. These precursors are expected to develop into healthy adult cells, restoring normal functions.
Another type of treatment strategy involves removing millions of disease-carrying stem cells and
genetically curing them correcting the disease-causing genetic defect and then transplanting
the healthy cells back into the patient.
A UCLA team is developing such a gene therapy to cure sickle cell disease (SCD), the debilitating
disorder that affects nearly 100,000 Americans, weakening many and often killing them before the age
of 40. The genetic disease causes red blood cells to take on a sickle shape, clogging blood vessels
and producing episodes of excruciating pain.
Most people with SCD have some type of brain blood vessel problem by the time they are 20, and
about one in seven have severe strokes. Current medical treatments can provide short-term relief, but
the disease leads to progressive deterioration in organ function. In even its milder forms, SCD
prevents a normal blood supply, starving cells of oxygen and leading to episodes of severe bone and
abdominal pain, breathing problems and progressive kidney damage.
Like many genetic disorders, SCD affects certain populations more than others. The single inherited
defect in a single gene that causes the disease occurs more frequently in African Americans, with one
in 500 people afflicted. About 5 percent of SCD patients in California are Hispanic Americans.
Donald Kohn, director of the Human Gene Medicine Program at UCLA and a scientist with UCLAs Eli
and Edythe Broad Center for Regenerative Medicine and Stem Cell Research , received a $9
million Disease Team grant from the California Institute for Regenerative Medicine (CIRM) to
develop a stem cell treatment for the disease. For SCD patients, his team seeks to genetically correct
their bone marrow adult hematopoietic stem cells those cells that give rise to all types of blood cells
by adding a hemoglobin gene that blocks the sickling of the red blood cells. The healthy stem cells
then will be transplanted back into the patients.
The strategy has the potential to permanently cure the illness with far less toxicity and risk than a bone
marrow transplant from another person.
Kohn and his colleagues have shown in the laboratory that they can take cells from an SCD patient
and genetically alter them to prevent sickling. After additional laboratory research, they will seek FDA
approval to demonstrate that genetically corrected human bone marrow stem cells can be transplanted
into SCD patients and enable them to make normal red blood cells.
Kohn feels confident that his team can meet its target: human clinical trials within four years.
This will be the sixth gene therapy clinical trial I have directed, he said. Its a technically complex
project, but I think the timeline is realistic. There is a desperate need for new approaches. Its a very
bad disease for many patients, and current therapies havent made patients much better.
Astrocytes for ALS

A UC San Diego program to develop a treatment for amyotrophic lateral sclerosis, or Lou Gehrigs
Disease, received about $11 million in a CIRM-funded Disease Team grant. Larry Goldstein, professor
of cellular and molecular medicine and director of the UC San Diego Stem Cell Program, heads the
effort. Like UCLAs Kohn, Goldstein plans to advance this research to a therapy that can move to
clinical trials in just a few years.
People with ALS experience a rapidly progressive weakness, muscle atrophy and severe respiratory
deficit among other grim effects, and most die after two to five years. The disease is caused by
degeneration of neurons in the spinal cord and the brain.
No cures for ALS have been developed, but Goldstein and colleagues at UC San Diego and other
institutions have found strong evidence that the disease not only damages neurons but also
astrocytes, a type of cell known to provide critical support for neurons. The teams studies in a rat
version of ALS shows that injecting healthy versions of astrocytes into the spinal cord may rescue
motor neurons and stop, or at least slow down, the devastating damage.
Its the death of motor neurons that leads to paralysis, but we think damaged astrocytes are a key part
of the disease, Goldstein says. They normally provide nutrients to neurons and maintain an
environment that is essential for neurons to survive and function properly.
Goldstein's team wants to tweak human embryonic stem cells to become astrocyte precursors, and
transplant these stem cells into spinal cords of ALS patients to at least partially restore normal function.
The team must convert stem cells to astrocyte precursors in a quantity large enough to be clinically
useful. Millions are needed. Research with animals should help determine roughly how many stem
cells would be needed for humans.
As director of UC San Diegos stem cell program, Goldstein supports efforts to streamline these early
days of research-into-treatments. His ALS project will use a single embryonic cell line for many
different patients in order to retain control of safety and efficacy. One cellular product can be
extensively tested and used on many patients, he says.
Goldstein champions the use of human stem cells to allow researchers to seek treatments by studying
diseases in a dish.
Animal models are important for understanding the basic principles of cell function, but animals are
not human, and diseases impact different types of organisms differently, he says. By testing drugs
and other treatments directly on human cells we are very hopeful we can more quickly get to the payoff
of therapies and cures.