Stem cell sorting gets mega boost from micro technology


By John Carroll

When research scientist Bruce E. Torbett is isolating stem cells from blood in his laboratory at The Scripps Research Institute’s Department of Molecular and Experimental Medicine, he relies on a hefty device that costs about $30,000. An antibody is used to identify the cells and attach them to magnetic beads, which then pass by a magnetic column that demagnetizes them and allows the cells to be harvested.

It’s a time-consuming and expensive process, taking hours of lab time. It’s also an absolute necessity for anyone studying the therapeutic qualities of stem cells.

For companies developing stem cell therapies for widespread use against disease, though, that kind of painstaking procedure looms like a technological roadblock. To remove the barrier, Durham, N.C.-based Aldagen has hooked up with specialty MEMS manufacturer Innovative Micro Technology to begin beta testing a new machine - the Aldesorter - that’s designed to make the technology cheaper, faster and a lot easier to use.

“Current technology was built really for the research market,” said Ed Field, the president and COO of Aldagen, which is researching the use of adult stem cells for the purpose of repairing human tissue, a field that includes rebuilding blood vessels in cardiac patients.

With several stem cell therapies in the pipeline, Field can easily look beyond the research stage to a period when these treatments will become available to large populations of patients. At that point, he says, slow speeds and large machines simply won’t cut it anymore.

“What we were looking for was a very simple desk-top solution where we could provide much faster isolation of these stem cells populations and also have a sterile sorting path so you can throw it away and put in a new disposable for the next patient,” said Field.

Within the Aldesorter, shown here, microfluidic devices isolate the stem cells needed for a treatment. Image courtesy Innovative Micro Technology
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The collaboration marries IMT’s expertise with microfluidics with Aldagen’s chemical reagents that are required to mark and isolate pure stem cell populations from cord blood and bone marrow. Together, they plan to turn out a new version of IMT’s cell sorter specifically to isolate adult stem cells for treatments aimed at a range of diseases that includes chronic heart failure, peripheral vascular disease, leukemias and genetic enzyme deficiencies.

“It is,” said IMT CEO John Foster, “a race car tuned for Aldagen’s application.”

IMT has been working with stem cell isolation technology for the past four years, says Foster, when it was originally funded by the Defense Advanced Research Projects Agency.

In the Aldesorter, IMT’s chips work with an external laser that excites a fluorescent light from cells tagged by a universal stem cell marker, along with a high-speed actuator valve and microfluidics to isolate the stem cells needed for a treatment. And it’s being developed so that the chips can be replaced for every new patient, providing a sterile process for each new patient.

If they’re successful, they can help change the way the stem cell isolation works.

“The Aldagen group and IMT are proposing a different way” to isolate stem cells, said Torbett, “using a proprietary dye that stains the same stem cell population, but with no beads and no antibodies, going through a microfluidic chip at a fast rate which is much quicker to isolate the cells.

“Conventional sorting would be slower than the chip type of technology,” he added. “MEMS is quite rapid. The argument is for another modality and a more rapid method for isolation. What had taken five hours to separate might now take an hour.”

The IMT cell sorter chip showing input, sort/keep, and waste tubing. All microfluidics are contained within the chip for sterility and disposability. Image courtesy Innovative Micro Technology
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That would be an exciting advance that would not only help provide the therapy to patients, says Torbett, but also speed research in the field as well. It’s not a technological revolution, he adds, and it’s likely to take several years to fully prove itself. But it is an important incremental step, and one that a number of technology companies in the field are also exploring.

“I think that these kinds of devices would be useful, cheaper than current devices,” Torbett said. “There are things that have to be worked out, but it would be an enabling technology.”

For Aldagen, the work is critical to developing stem cell therapies, where stem cells are collected from a patient and then reinfused, readily available to treat diseases.

“We’re looking at heart failure ischemia, where there are hundreds of thousands of patients,” said Field. “The current machine could do one person a day. The Aldesorter can handle five to six patients a day per machine.”

“You can sort stem cells today and use the reagents that Aldagen is using to come up and get a great supply of stem cells,” said Foster. “The problem is the speed and sterility of the path which we are solving to make it a clinical tool.”

Drawing stem cells from bone marrow, for example, requires the ability to isolate one percent of all the cells in the bone marrow, says Foster. “That’s not a needle in the haystack, but it isn’t easy.”

Having a fast method to sort a patient’s stem cells on the spot will be particularly critical in an acute therapy.

Stem cells, above, flow through an IMT cell sorter microfluidic channel. Image courtesy Innovative Micro Technology
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“You may want to take the Aldesorter, draw marrow, isolate the stem cells and put them right back into the heart,” said Field. “It makes it easier to get into these chronic populations and in acute settings for trauma or heart attack and stroke. Because the Aldesorter is quick, we can begin to explore the use of stem cells in those markets.”

The final business model hasn’t been crafted yet, says Field, but it may be that the best way to commercialize technology like the Aldesorter will be to give the machine away and sell the disposable chips to users. And Foster isn’t ruling out broader applications as the stem cell field develops.

“Aldagen is our partner for the clinical use of these stem cells,” said Foster. “There may be other applications for cell sorting.”

Aldegan was recently preparing to unveil Phase I data on the Aldesorter. From there, says Field, they can go to the FDA and start a countdown on a follow-up study that can be used to seek FDA approval in 2008. And Field is confidently predicting that Aldagen will be in the forefront of the developers working in the adult stem cell field.

“We believe that the first commercialization of stem cells will be in the adult setting,” said Field. “Embryonic stem cells will take a long time to develop, with some tough ethical and political issues. In the adult space, there’s a faster path to commercialization.”