New research from Iowa State University detailing the creation of blood stem cells was published in the scientific journal Nature Communications on Sept. 6th.
WVIK spoke with co-author Clyde Campbell, an assistant genetics, development, and cell biology professor at Iowa State University. He works with fellow professor and lead researcher Raquel Espin Palazon in their cell biology lab in Ames, Iowa.
Palazon discovered a decade ago that embryos must switch on inflammatory signaling pathways to produce blood stem cells. Now, the duo is learning that the switch can be paused, allowing the embryo to create hundreds, possibly more, stem cells. The finding has huge implications for treating blood disorders like leukemia, lymphoma, and anemia, where patients need an applicable match to donate stem cells out of their bone marrow, which is a cumbersome process.
"There was gaps in the field that needed to be addressed when making blood stem cells. Some of that is the fact that just the efficiency of the process was extremely low. And then when we are able to make those cells in a laboratory setting, the ability to expand those cells were very low as well," Campbell said in a phone interview with WVIK. "And it really just came down to kind of an incomplete understanding of the natural developmental signals that allow us to make these cells in our body."
Campbell says a person's body replaces hundreds of millions of blood cells in just one minute. These cells come from stem cells in the bone marrow, all made at once during the fetus's early development.
The researchers from Iowa State University say a family of proteins (NF-kB P65) activates the signaling protein to release the newly created cells to the rest of the body.
"And so this is a family member that's been studied in depth in terms of inflammatory response and cancers. However, its function, like what it's actually doing in the context of development, was never known. So through this study, we actually assigned a brand new function to a very well-studied protein, P65," Campbell said.
Campbell and Palazon use zebrafish in their research to study the inflammatory signaling pathway. According to Campbell, fish, unlike mammals, lay their eggs instead of developing within the womb, so it's not invasive on the species to study.
"Nature is great. Once it creates something, it doesn't recreate multiple ways of doing it, so there's a very high conservation in terms of the signals required to make blood stem cells," Campbell said. "And zebrafish develop externally, so we can literally watch the formation of stem cells in a live zebrafish embryo from the time of when they're specified to the time when they actually emerge. So it's a phenomenal model. And when we start to look at signals that are associated with inflammation, it's really important to minimize any trauma or interaction with the tissue [as much] as possible. And the zebrafish allow us to do that."
The researchers inserted fluorescence-producing reporter genes to make the selected types of protein and gene expression visibly glow to allow real-time tracking. (Seen in the image attached to the story) The discovery that inhibiting the protein from stopping stem cell production and releasing the cells could rev up the production of stem cells was unexpected for the researchers.
"One of the moments in my scientific career that I'm probably most proud of because it's just one of those things that, that you just don't expect to see. And, the expansion of the cells that we did observe is something that has never been documented in our field. So, seeing it for the first time under the microscope really, really knocked me out of my chair, to be honest," Campbell said.
Campbell says the discovery of producing hundreds of blood stem cells can help the medical treatment of cancers by stopping cancer cells from proliferating, detaching, and ultimately metastasizing. Though it will take time for the researchers to figure out how to induce the same results from zebrafish to humans.
Their research was funded by a $2 million grant from the National Institutes of Health over five years, which allowed them to shadow researchers at the Children's Hospital of Philadelphia.
"...[W]ho are really the leaders in this laboratory-derived stem cells for therapeutic use," Campbell said. "And so we were able to go there for a month and really learn from the best people in the world [on] how to do this. And then after that, we were able to gather all the equipment to run this in-house here at Iowa State. So, we're currently in the process of initiating our own... Our own lab-grown stem cells in hopes of optimizing kind of the recipe or the protocol to generate more of these blood stem cells. So we're super excited about the next portion, and it also relates to another grant that we'll be putting out in a few months to hopefully help fund the continuation of these findings."
Campbell says the lab should be up and running by the end of this year.
