CIRM Scientists Discover Key to Blood Cells’ Building Blocks

Our bodies generate new blood cells—both red and white blood cells—each and every day. But reproducing that feat in a petri dish has proven far more difficult.

Pictured: sections from zebrafish embryos. Blood vessels are labeled in red, the protein complex that regulates inflammation green and cell nuclei in blue. The arrowhead indicates a potential HSC. The image at bottom right combines all channels. [Credit: UC San Diego School of Medicine]

Pictured: sections from zebrafish embryos. Blood vessels are labeled in red, the protein complex that regulates inflammation green and cell nuclei in blue. The arrowhead indicates a potential HSC. The image at bottom right combines all channels.
[Credit: UC San Diego School of Medicine]

But now, scientists have identified the missing ingredient to producing hematopoietic stem cells, or HSC’s—the type of stem cell that gives rise to all blood and immune cells in the body. The results, published last week in the journal Cell, describe how a newly discovered protein plays a key role in generating HSC’s in the developing embryo—giving scientists a more complete recipe to reproduce these cells in the lab.

The research, which was led by University of California, San Diego (UCSD) professor David Traver and supported by a grant from CIRM, offers renewed hope for the possibility of generating patient-specific blood or immune cells using induced pluripotent stem cell (iPS cell) technology.

As Traver explained in last week’s news release:

“The development of some mature cell lineages from iPS cells, such as cardiac or neural, has been reasonably straightforward, but not with HSCs. This is likely due, at least in part, to not fully understanding all the factors used by the embryo to generate HSCs.”

Indeed, the ability to generate HSCs has long challenged scientists, as outlined in a CIRM workshop from last year. But now, says Traver, they have found a crucial piece to the puzzle.

Specifically, the researchers investigated a signaling protein called tumor necrosis factor alpha—or TNFα for short— a protein known to be important for regulating inflammation and immunity. Previous research by this study’s first author, Raquel Espin-Palazon, and others also discovered it was related to the healthy function of blood vessels during embryonic development.

In this study, Traver, Espin-Palazon and the UCSD drilled down even further—and found that TNFα was required for the normal development of HSCs in the embryo. This surprised the research team, as the young embryo is generally considered to be sterile—with no need for a protein normally charged with regulating immune response to be switched on. Explained Traver:

“There was no expectation that pro-inflammatory signaling would be active at this time or in the blood-forming regions.”

While preliminary, establishing this relationship between TNFα and HSC formation will be a boon to researchers looking for new ways to generate large quantities of healthy, patient-specific red and white blood cells for those patients who so desperately need them.

Learn more about how stem cell technology could help treat blood diseases in our Thalassemia Fact Sheet.

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