Scientists Reprogram Mature Blood Cells to Generate Elusive Blood Stem Cells

Image: Derrick Rossi [credit: Boston Children’s Hospital]

It’s one of regenerative medicine’s most sought-after goals, but also one of the most difficult to reach: figuring out how to produce blood-forming hematopoietic stem cells, or HSCs. But now, researchers at the Harvard Stem Cell Institute at Boston Children’s Hospital have identified a stem cell-based technique that has the potential to do just that.

These types of cells, which form the basis of all our various blood cells, are in high demand for much-needed bone marrow transplants that treat various blood disorders such as leukemia. However, in nature HSCs are extremely rare. And previous stem cell-based therapies have been unable to generate HSCs that are suitable for transplantation. For example, check out this 2008 workshop whereby Cornelius Murre explains the difficult process of transforming stem cells into blood cells. Those difficulties persisted and still perplexed researchers attending an international workshop CIRM convened on the topic last summer.

Enter Boston Children’s Hospital’s Derrick Rossi. An expert in stem cell biology, Rossi was able to physically reprogram mature blood cells from mice into cells that looked and acted just like HSCs. They describe their results in the journal Cell. They called these new cells induced HSCs, or iHSCs. As Rossi explained in a recent news release:

“Blood cell production invariably goes in one direction: from stem cells, to progenitors, to mature…cells. We wanted to reverse the process and derive HSCs from differentiated blood cells using transcription factors that we found were specific to HSCs.”

These ‘transcription factors’ came in the form of eight genetic switches that were inserted into the mice’s mature blood cells in order to kick-start the cellular reprogramming process. The results were iHSCs in mice that were capable of recapitulating all blood cell types. As the study’s co-author Stuart Orkin added in the same news release:

“In the blood research field, no one has the conditions to expand HSCs in the tissue culture dish. Instead, by letting the reprogramming occur in [the cells of] mice, Rossi takes advantage of the signaling and environmental cues that HSCs would normally experience.”

While promising, there is still more work to be done, Rossi adds. For example, while the technique works in mice, there may be a different set of factors required to transform human blood cells into iHSCs. But Rossi and his research team have been bolstered by the results of this study and what it could mean for the future of bone marrow transplants—a future in which the patient’s own mature blood cells can be transformed into cells suitable for transplantation.

Anne Holden

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