Numerous stem cell-based therapies are currently under investigation, including an FDA-approved clinical trial focused on employing neural stem cells (NSCs) in delivering drugs targeting invasive brain tumors. “The ability to monitor the time course, migration and distribution of stem cells following transplantation into these patients would provide critical information for optimizing treatment regimens,” Dr. Moats said. “However, no effective cell-tracking methodology had yet garnered clinical acceptance.”
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In an article featured in the latest issue of STEM CELLS, a research group from Stanford University describes a novel regimen for quashing this immunologic barrier — a short-course treatment with two costimlation-adhesion blockade agents, allowing engraftment of transplanted differentiated stem cells and their prolonged survival in tissue.
"Inducing immune tolerance to human embryonic stem cell graft is critical for the clinical success of regenerative medicine,” commented Dr. Joseph Wu, M.D., Professor of Medicine and Radiology at the Stanford University School of Medicine. “We have realized, however, that traditional immunosuppressive therapies used to prevent solid organ rejection, such as calcineurin inhibitors and corticosteroids, are insufficient to prevent human embryonic stem cell rejection following transplantation.”
However, a new study released today in STEM CELLS Translational Medicine indicates that endothelial precursor cells, which are found in the bone marrow, umbilical cord blood, and as very rare cells in peripheral blood, could make a significant difference for these patients’ recovery — even in the later stages of stroke. In animal studies, the treatment minimized the initial brain injury and helped repair the stroke damage.
“Previous studies indicated that stem/progenitor cells derived from human umbilical cord blood (hUCB) improved functional recovery in stroke models,” noted Branislava Janic, Ph.D., a member of Henry Ford Health System’s Cellular and Molecular Imaging Laboratory in Detroit and lead author of the study. “We wanted to examine the effect of hUCB-derived AC133+ endothelial progenitor cells (EPCs) on stroke development and resolution in rats.”
“In this work, we describe a highly innovative gene therapy approach, which is being developed along with the NIH and the FDA. Specifically, our group has developed an allogeneic neural stem cell line that is a carrier for a virus that can selectively infect and break down cancer cells,” explained Dr. Lesniak, the University of Chicago’s director of neurosurgical oncology and neuro-oncology research at the Brain Tumor Center.
The stem cell line, called HB1.F3 NSC, was recently approved by the FDA for use in a phase I human clinical trial.
GBM remains fatal despite intensive treatment with surgery, radiation and chemotherapy. And while cancer-killing viruses have been used in clinical trials to treat therapeutically resistant and infiltrative tumor burdens throughout the brain, “there were major drawbacks,” Dr. Lesniak explained.
As such, it could lead to a purer, safer therapeutic grade of stem cells for use in regenerative medicine.
The discovery of iPSCs holds great promise for regenerative medicine since it is possible to produce patient-specific iPSCs from the individual for potential autologous treatment — that is, treatment using the patient’s own cells. This avoids the possibility of rejection and numerous other harmful side effects.
CD34+ cells are a type of blood stem cell that has been linked to proliferation. However, collecting enough CD34+ cells from a patient to produce an adequate amount of blood usually requires a large volume of blood to be taken from the patient. But scientists found a way around this, as outlined in the new study conducted by researchers in the Department of Medicine and Institute for Human Genetic, University of California-San Francisco. They were led by Yuet Wai Kan, M.D., FRS, and Lin Ye, Ph.D.
In addition, the research demonstrates that the transplanted organ retained its immunologically privileged state during a subsequent transplantation into another naïve recipient.
“Dental cavities and inflammation of the surrounding pulp is a challenging public health issue, as tooth decay not only can cause a patient great pain but it also can lead to other serious health issues including heart disease,” explained Misako Nakashima, DDS, Ph.D., of the National Center for Geriatrics and Gerontology in Obu, Japan. “Generally we treat deep cavities by capping the tooth and removing any inflamed pulp surrounding it. But this has limited success and the problem frequently progresses until the tooth must be removed.”
But now a research team reports that it has developed a way to speed up the process. Their work, which involves the creation of a highly stable and sensitive liver stem cell model, is reported in the latest issue of STEM CELLS Translational Medicine.
“Liver toxicity is the second most common cause of human drug failure,” explained David Hay, Ph.D., of the University of Edinburgh’s MRC Centre for Regenerative Medicine, who led the team made up of university colleagues and scientists from Bristol-Myers Squibb, Princeton, N.J. “But one major bottleneck in safety testing new drugs has been finding a routine supply of good quality primary human hepatocytes from the desired genetic background.”
Researchers at the Leiden University Medical Center’s Department of Immunohematology and Blood Transfusion in Leiden, The Netherlands, led by Helene Roelofs, Ph.D., conducted the study. They were seeking an alternative to bone marrow for stem cell therapies because of the low number of stem cells available in marrow and also because harvesting them involves an invasive procedure.
“Adipose tissue is an interesting alternative since it contains approximately a 500-fold higher frequency of stem cells and tissue collection is simple,” Dr. Roelofs said.
“Moreover,” Dr. Sara M. Melief added, “400,000 liposuctions a year are performed in the U.S. alone, where the aspirated adipose tissue is regarded as waste and could be collected without any additional burden or risk for the donor.”
Many medical experts have long believed that neural stem cells (NSCs) have great potential for treating neurological diseases. However, the problem is that just a small number of NSCs can be transplanted into the brain, yielding relatively low levels of new cell growth and, thus, a limited effect. “We wanted to investigate whether using a specific population of neural cells would help increase the number of mature brain cells that the stem cell graft yields,” Dr. Wolfe explained.
The team began by harvesting NSCs from the brains of baby mice and used a process known as fluorescence activated cell sorting to identify cells with markers for CD15, a type of carbohydrate found on a cell’s surface that plays an important role in cell migration, adhesion and in the growth factor signaling involved in cell maintenance and differentiation.