In cell therapy, doctors reprogram some cells from patients’ skin or blood to create induced pluripotent stem cells. They convince these stem cells to transform into progenitor cells to treat spinal cord injury. These progenitors are then transplanted back into the patient to regenerate part of the injured spinal cord. However, pluripotent stem cells that do not fully become progenitors can form tumors.
Scientists from MIT and the Singapore-MIT Alliance for Research and Technology have developed a small device to improve cell therapy treatments with greater safety and effectiveness. They developed a microfluidic cell sorter to remove undifferentiated cells without damaging fully formed progenitor cells.
This newly developed device can sort more than 3 million cells per minute without special chemicals. In the study, scientists discovered that by combining many devices, more than 500 million cells per minute can be classified.
Pluripotent stem cells were generally larger than the progenitor cells derived from them. This happens because pluripotent stem cells have many genes that have not been turned off in their nucleus. As these cells specialize in specific functions, they suppress many genes that are no longer needed, reducing the size of the nucleus. The microfluidic device takes advantage of this size difference to sort cells.
The plastic chip contains small channels that create an entrance for cells to enter, a spiral path, and four exits where cells of different sizes are collected. When cells pass through the spiral at high speeds, various forces, including centrifugal forces, push them. These forces help gather cells at a specific point in the fluid stream based on their size, effectively separating them into different outlets.
The researchers found that they could improve the performance of the classifier by running it twice. First, they operate it at a slower speed, causing more giant cells to stick to the walls while smaller cells are separated. Then they run it faster to separate the larger cells.
The device works similarly to a centrifuge, but does not require human intervention to collect the sorted cells.
The device could remove almost 50% of the largest cells in a single pass. Furthermore, the device does not use any filtration. The limitations of filters are that they clog or break down over time, so a device without filters can be used for much longer.
Having demonstrated success on a small scale, researchers are now moving on to larger studies and animal models to determine whether the purified cells perform better when introduced into living organisms.
- Tan Dai Nguyen, Wai Hon Chooi, Hyungkook Jeon and others. Label-free, high-throughput removal of residual undifferentiated cells from iPSC-derived spinal cord progenitor cells. Translational stem cell medicine. DOI: 10.1093/stcltm/szae002