Stem cell device could have role in cancer treatment

By Dr Matt Wilkinson

- Last updated on GMT

Related tags Stem cells Stem cell Bone marrow

Researchers at the University of Rochester and StemCapture have
unveiled a new device technology that makes it possible to harvest
stem cells from the blood, bypassing the controversial use of stem
cells sourced from embryos.

The technology is also being developed into an anticancer implant that programmes cancer cells to die, potentially improving the prognosis for many cancer victims. If stem cell research develops the know-how, the technique may even yield implants that direct the body's own stem cells to differentiate into the required cells to repair damaged organs.

The new technology uses selectin molecules, which have a higher affinity for stem and cancer cells than other cells, to slow down the flow of specific cells along the length of the device relative to the majority of the blood.

These advances could enable more efficient access to adult stem cells, which are not covered by the legislative restrictions on embryonic stem cells, which have caused many bureaucratic problems in US-based stem cell research. The lack of a pure source of stem cells often hampers research into this potentially crucial therapeutic source.

Michael King, associate professor at the University of Rochester and founder of StemCapture, has been pursuing these new medical devices since he started his own lab at the University of Rochester in 2002. The adhesion technology originated while King was working for Daniel Hammer at the University of Pennsylvania on the biological adhesion of cells.

During inflammatory responses selectin molecules are mobilised to the surface of cells on the blood vessel wall and bind to the sialyl lewis X (SleX) carbohydrate groups on the cell surface proteins exhibited on the surface of stem cells, cancer cells and white blood cells.

Different cells present different proteins at their surfaces and these proteins affect how strongly the SleX groups can bind to the selectin molecules.

Crucially, both stem cells and cancer cells bind to selectins and allow them to be separated from the bulk of blood cells.

These findings have led to the conception of two devices being developed by King and his start-up company StemCapture; one for the enrichment of stem cells and another to kill cancer cells.

As bone marrow stem cells bind strongly to selectin molecules, King has formulated a device that allows the enrichment of stem cells from the blood. Currently in use as an ex vivo​ device, a blood sample can be run through a plastic tube coated with selectins that stick blood cells to the tube with 40 per cent being stem cells.

Typical centrifugation stem cell separation techniques yield stem cells in about one per cent purity, the majority of the collected cells being blood cells.

This non-controversial way of collecting stem cells should allow more efficient stem cell research whose reliability often relies on the relative abundance of stem cells compared to the number of contaminating cells that may interfere with the results.

Studies in the group by coworkers Joel Wojciechowski and Srinivas Narasipura have shown that the technique be used to collect adult stem cells that can still differentiate properly after collection.

A stem cell enrichment device could be quickly licensed due to the relatively short regulatory process for medical devices.

Organ repair

King envisages a future in vivo​ device that would allow stem cells to be enriched in a vascular shunt device close to a problem organ and using, as yet un-clarified differentiation factors, tell the cells to become the cell types needed to repair the organ.

Discussing the benefits of programming stem cells in the vicinity to a problem, King said; "one of the problems with stem cell therapies is that only about five per cent go where they are supposed to, which is a problem as there is a fine line between stem cells and cancer cells."

Cancer killer

A similar mechanism has been applied to create a cancer-killing implant, which is currently being tested in preclinical trials on rats. The device consists of a plastic tube coated with selectins and an anticancer agent, TNF-related apoptosis ligand (TRAIL).

TRAIL is a naturally occurring protein, which induces apoptosis or cell suicide in cancer cells with a high degree of specificity and is currently in various clinical trials.

The selectin surface causes the cancer cells to come into contact with the anchored TRAIL molecules that programme them to die as they flow through the shunt. King believes that it should be fairly simple to scale up the device to human size, for use as an arterial venular shunt in the arm.

King said: "the cancer cells don't need to stick to the surface before apotosis, but if they do the bodies own white blood cells clean them out - meaning this can be a more long-term implant.""StemCapture has begun the regulatory process and we are focussing now on preclinical trials and are optimistic that we can initiate human trials in two years from now."

Related topics Preclinical Research

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