Bone marrow transplants are a common treatment for certain conditions related to the blood, but the patient's immune system can often react badly to the foreign cells and attack them. Mesenchymal stromal cells (MSCs) may help, but they too can be cleared out by immune cells. Now, a Harvard team has shown that coating MSCs in a thin hydrogel can protect them, making bone marrow transplants more successful.
Stem cells that make blood are found in the bone marrow, which is why bone marrow transplants could help people with blood cancers or certain metabolic disorders. The problem of course is that the immune system can recognize transplanted tissue as foreign, and in a misguided attempt to help, it attacks the new cells. MSCs are known to regulate the immune system by secreting certain compounds, which in turn might keep it from attacking the transplant – but they too are vulnerable to being cleared out of the body.
So the team set out to make MSCs hardier and, in turn, let them protect bone marrow transplants from an overzealous immune system. The team is made up of researchers from several Harvard schools like the Wyss Institute, the School of Engineering and Applied Sciences (SEAS) and the Harvard Stem Cell Initiative (HSCI).
In a previous study, the team used a microfluidic device to coat MSCs with a thin layer of hydrogel, which they called microgels. These cells were able to stay inside test animals far longer than uncoated MSCs.
For the new study, the researchers improved the recipe of the microgel, making it stiffer so that the immune system had an even harder time clearing it out. At the same time, they made sure that being encapsulated didn't interfere with the cells' secretion or other functions, and the coated cells were then cultured to help them produce more.
These microgels were found to survive five times longer in mice than the earlier microgel, and an order of magnitude longer than bare MSCs. In another test, they activated the immune system to attack the cells by incubating them in fetal bovine serum. As expected, that did clear more of the MSCs than before, but these coated MSCs still held out five times longer than uncoated ones.
Next the team injected the encapsulated MSCs into mice that already had a heightened immune response against them, and found that they still performed better than bare MSCs. This test was designed to mimic human patients who get several stem cell infusions, which can build up an immune response over time.
And finally, in the main test, the researchers injected both bone marrow and the MSC microgels into mice, to see how well the latter protected the former. Half of the bone marrow was immune-compatible and the other half wasn't (allogeneic). The team found that after nine days, mice that received MSC microgel had twice as much of the allogeneic cells in their bone marrow, compared to mice that didn't receive the MSCs. Again, the coated MSCs also performed better than bare MSCs.
"One of the strong points of this work is that it uses a completely non-genetic approach to dramatically increase cell survival in transplant contexts, where it's sorely needed," says David Mooney, lead author of the study. "This technology nicely complements genetic engineering approaches, and in fact could be more efficient than attempting to directly modify immune cells themselves."
The research was published in the journal PNAS.
Source: Wyss Institute
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