The microfluidic cell sorter, built by researchers at the Massachusetts Institute of Technology (MIT) and the Singapore-MIT Alliance for Research and Technology, would be used before cell therapy.
In that process, doctors create ‘induced pluripotent stem cells’ by reprogramming skin or blood cells taken from a patient. These are then coaxed into becoming progenitor cells, which are destined to become spinal cord cells. The progenitors are then transplanted back into the patient.
These cells can regenerate part of the injured spinal cord. Pluripotent stem cells that do not fully change into progenitors can form tumours, however.
The new cell sorter can remove about half of the undifferentiated cells – those that can potentially become tumours – from a batch without any damage to the fully-formed progenitor cells, the MIT team said.
The device, which does not require special chemicals, can sort more than 3m cells per minute. The researchers also showed that chaining many devices together can sort more than 500m cells per minute, making it a more viable method to eventually improve the safety of cell therapy treatments.
Clinicians and researchers often seek to identify and remove cells by looking for certain markers on their surfaces, but so far they have been unable to find a marker that is specific to undifferentiated cells. Other methods use chemicals to selectively destroy the cells, but these treatments may be harmful to differentiated cells.
The high-throughput microfluidic sorter, which can sort cells based on size, was developed by the Critical Analytics for Manufacturing Personalised Medicine (Camp) team at the Singapore-MIT Alliance. It has previously been used for sorting immune cells and mesenchymal stromal cells (another type of stem cell), and now the team is expanding its use to other stem cell types, such as induced pluripotent stem cells.
The team discovered that pluripotent stem cells tend to be larger than the progenitors derived from them. The microfluidic device uses this size difference to sort them.
Microfluidic channels in the small coin-sized plastic chip form an inlet, a spiral, and four outlets that output cells of different sizes. As the cells are forced through the spiral at very high speeds, various forces, including centrifugal forces, act on the cells. These forces counteract to focus the cells in a certain location in the fluid stream. This focusing point is dependent on the size of the cells, effectively sorting them through separate outlets.
The researchers found they could improve the sorter’s operation by running it twice, first at a lower speed so larger cells stick to the walls and smaller cells are sorted out, then at a higher speed to sort out larger cells.
The chip that contains the microfluidic cell sorter could be mass-produced in a factory at “very low cost”, the MIT announcement said, so the device could be easy to implement at scale.
“Even if you have a life-saving cell therapy that is doing wonders for patients, if you cannot manufacture it cost effectively, reliably, and safely, then its impact might be limited. Our team is passionate about that problem – we want to make these therapies more reliable and easily accessible,” said researcher Professor Jongyoon Han.
The team is now starting larger studies and animal models to see if the purified cells function better in vivo.
The work was published in Stem Cells Translational Medicine.
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