Stem Cell-Conventional Treatment Combo Offers New Hope in Fighting Deadly Brain Cancer


A new type of treatment that combines neural stem cells with conventional cancer fighting therapies shows promise in animal studies for the most common and deadliest form of adult brain cancer — glioblastoma multiforme (GBM). The details are revealed in a groundbreaking study led by Maciej Lesniak, M.D., that appeared in the journal STEM CELLS Translational Medicine.

“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 used is a neural stem cell line called HB1.F3 NSC. The US Food and Drug Administration has recently approved this cell line for use in a phase I human clinical trial.

Glioblastoma multiforme remains fatal despite intensive treatment with surgery, radiation and chemotherapy. Cancer-killing viruses have been used in clinical trials to treat those tumors that resist treatment with other therapies and infiltrate throughout the brain. Unfortunately, according to Lesniak, this therapy was subject to some “major drawbacks.”

“When you inject a virus into a tumor alone (without a carrier, like NSC), the virus stays at the site of the injection, and does not spread. Moreover, our immune system clears it. By using NSCs, we can achieve a widespread distribution of the virus throughout the tumor mass, since the NSC travel. Also, they act like a stealth fighter, hiding the virus from the immune system.” Lesniak and his co-workers used NSCs loaded with a novel oncolytic adenovirus. This virus selectively targets glioblastoma multiforme in combination with chemo-radiotherapy. Using this strategy, Lesniak’s team was able to overcome the limitations associated with anticancer viral therapies.

Using mice that had glioblastoma multiforme, the research team showed that their neural stem cell line, which is derived from human fetal cells, significantly increased the median survival time of the mice beyond conventional treatments alone. The addition of chemo-radiotherapy further enhanced the benefits of this novel stem cell-based gene therapy approach.

“Our study argues in favor of using stem cells for delivery of oncolytic viruses along with multimodal chemo-radiotherapy for the treatment of patients with glioblastoma multiforme, and this is something that we believe warrants further clinical investigation,” Dr. Lesniak concluded.

Lesniak’s team is completing final FDA-directed studies. He expects to start a human clinical trial, in which a novel oncolytic virus will be delivered via NSCs to patients with newly diagnosed glioblastoma multiforme, early in 2014.

Treatment of glioblastoma multiforme depends on novel therapies,” said Anthony Atala, M.D., Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “This study establishes that a combination of conventional and gene therapies may be most effective and suggests a protocol for a future clinical investigation.”

Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate The Healing of Large Skin Wounds


Bioprinting is a contrived term that describes the deposition of cells on surfaces by means of inkjet printer technology. Because the inkjet squirts small quantities of ink in a precisely specified shape and pattern, inkjets can be adapted to the application of cells on living surfaces or on scaffolds fashioned in the form of living organs or tissues.

Shay Soker at the Wake Forest Institute for Regenerative Medicine in Winston-Salem, North Carolina, has published a remarkable study that uses inkjet technology to deposit stem cells over large skin wounds. His study shows that bioprinting is a potentially very efficient way to deliver stem cells to wounds.

There are on estimate a half a million burns treated in the US each year. Extensive burns and so-called full thickness skin wounds are usually very traumatic for patients. The mortality rates of burns are about 5% and cost ~2 billion per year. Present strategies for treating burns tend to produce extensive scarring and relatively poor cosmetic outcomes.

Tissue engineering approached have the potential to provide more effective treatments for such injuries. Graft products such as Dermagraft and TransCyte from Advanced BioHealing and Apligraft from Organogenesis are cellularized graft products composed or a polymer scaffold that is seeded with cells. Unfortunately, these are expensive to make. Cell spraying and bioprinting, which deposits cells encased in hydrogel spheres all around the wound are a cheaper and potentially more attractive approach to wound therapy.

Soker’s team used stem cells from amniotic fluid and mesenchymal stem cells for this experiments. These stem cells were grown in culture, mixed in fibrin-collagen hydrogels, and bioprinted to surgically-produced wounds on the backs of hairless (nude) mice. The wounds all closed at approximately the same rate over a two-week period for those wounds treated with amniotic-fluid stem cells or mesenchymal stem cells. Wound closing was slow for those treated with only hydrogels.

Amniotic Fluid Stem Cells
Amniotic Fluid Stem Cells

After the wounds closed, biopsies of the wounds showed that the wounds that had been treated with amniotic fluid stem cells were filled with small blood vessels. Wounds bioprinted with mesenchymal stem cells did not have quite as many blood vessels as those seen in mice treated with amniotic stem cells, and those treated only with hydrogels had hardly any. However, when the biopsies were examined in detail to find the stem cells, they were not to be found. Therefore, the stem cells were not incorporated into the wounds, but induced healing through molecules that they secreted.

Not satisfied with this, Soker and his colleagues examined the gene expression patterns of the amniotic fluid stem cells and compared them to the gene expression patterns of mesenchymal stem cells. As expected, the amniotic fluid stem cells had oodles and oodles of growth factors. Fibroblast growth factors, Insulin-like growth factors, Vascular endothelial growth factor, Hepatic growth factor, and several others were made by amniotic fluid stem cells. Mesenchymal stem cells made their fair share of growth factors, but not nearly as many ans their amniotic fluid counterparts.

From these experiments, Soker concluded that even though bioprinting is a new technology, is can deliver cells effectively to surface wounds. Also, the stem cells do not directly contribute to the healing of the wound, but induce other cells to migrate into the wound and heal it. The delivery of bioprinted cells in hydrogels has the potential to rebuild a tissue from the ground up.

See Aleksander Skardai, et al., “Bioprinted Amniotic-Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds,” Stem Cells Translational Medicine 2012;1:792-802.