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Long-awaited “Trackable” Stem Cells Attack Patients’ Brain Tumors

Mon, 10/07/2013 - 11:57am
Cynthia Fox

The FDA has approved the first, long-awaited, and safe method for tracking stem cells in the human body. The approach could lead to dramatic advances in the area of regenerative medicine and cancer therapies.

“We are getting a positive response,” says Rex Moats of the UCLA Keck School of Medicine, lead investigator on a paper describing the work leading to the FDA-approved approach. “Clinical trials are now ongoing.”

Progress in many stem cell research areas has been impeded by an inability to track the cells in the human body. Researchers can track stem cells in animal models using potentially toxic labeling techniques. But humans must not be subjected to toxic labeling, for obvious reasons.

In a recent Stem Cells Translational Medicine, researchers with UCLA, the City of Hope National Medical Center, and the National Institutes of Health (NIH) reported on the many studies, done by many groups, that led to this first non-toxic stem cell tracking approach in humans.

The approach involves labeling stem cells with an element already at home in the human body: iron.

The paper describes the method as it was perfected in mouse models. To create the new FDA-approved labeling technique, the City of Hope group preloaded neural stem cells (NSCs) with ferumoxytol, an iron-oxide nanoparticle, along with the commonly used anti-coagulant heparin, and protamine sulfate. Ferumoxytol is already used to treat anemic (iron-low) kidney disease patients. The other two components ease the ferumoxytol into the cytoplasm of NSCs in a petri dish.

Rex Moats, PhD, UCLA Keck School of Medicine“Heparin very mildly breaks up surface glycosylation, and protamine sulfate complexes with the nanoparticles which aids their penetration across the membrane,” says Moats, who is director of the Sabin Institute Small Animal Imaging Research Center. “The NSCs do not take up the iron particles without the protamine sulfate and the heparin. Or at least, they greatly increase the uptake.”

The group then injected those now iron-flagged NSCs into mice with human brain cancer glioblastoma. The hope was the cells would be seen on MRI (which detects certain iron levels). Specifically, the hope was the cells would be seen homing in on the cancer cells.

For previous clinical and preclinical work by the group has established that some migrating NSCs pursue brain cancer cells, attracted by emitted growth factors. The group has been co-opting this quality in NSCs to use them as drug mules. That is, they genetically alter the NSCs to express enzymes that can activate cancer-killing pro-drugs when they migrate to tumors.

When the team placed the mice in small MRIs, the NSCs were indeed suddenly visible. The MRIs revealed the iron-flagged neural stem cells had homed in on the glioblastoma cells. After sacrificing the mice and performing a series of tests, they found the NSCs “were primarily detected in the peripheral areas of tumors and in association with invasive glioma cells,” the paper reports.

All this occurred safely. The iron was apparently at length flushed out of the bodies, as occurs with natural iron stores.

“The amount of iron delivered to the host was minimal compared with many naturally occurring (i.e. by ingestion), or exogenous, sources of iron (e.g. blood transfusions or iron therapy in chronic kidney disease),” the group wrote. The NSCs were deemed functional, not disabled by the minimal iron load.

There is an ongoing clinical trial utilizing this approach, says Moats. To date, three glioma patients were treated with NSCs containing a pro-drug activating enzyme, and the ferumoxytol/heparin/protamine sulfate labeling combo. “The preliminary data on the use of this methodology in humans will likely appear within the next six months,” says Moats.

Various members of Moats’ team are also officers or board members with TheraBiologics, a company formed to co-opt the tropism (attraction) that can occur between cancers and stem cells. TheraBiologics received an $18 million grant from CIRM, and two grants from the NIH, for its NSC therapies.

TheraBiologics holds an exclusive license from Harvard University to patents for harnessing stem cells to combat cancer. 

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