By watching how zebrafish embryos develop, scientists are starting to unravel the mystery of how the human body produces stem cells called HSCs.
They are found in bone marrow and in umbilical cord blood and are critically important because they can replenish the body’s supply of blood cells.
Leukemia patients have been successfully treated using HSC transplants, but medical experts believe blood stem cells have the potential to be used more widely.
Lead researcher Peter Currie, a professor at Monash University, says that understanding how HSCs self-renew to replenish blood cells is a “Holy Grail” of stem cell biology.
“HSCs are one of the best therapeutic tools at our disposal because they can make any blood cell in the body. Potentially we could use these cells in many more ways than current transplantation strategies to treat serious blood disorders and diseases, but only if we can figure out how they are generated in the first place. Our study brings this possibility a step closer,” he says.
A key stumbling block to using HSCs more widely has been an inability to produce them in the laboratory setting. The reason for this, suggested from previous research, is that a molecular “switch” may also be necessary for HSC formation, though the mechanism responsible has remained a mystery, until now.
In this latest study, published in the journal Nature, researchers observed cells in the developing zebrafish—a tropical freshwater fish known for its regenerative abilities and optically clear embryos—to gather new information on the signaling process responsible for HSC generation.
Using high-resolution microscopy, researchers recorded how these stem cells form inside the embryo.
When they played back the recordings, Currie says they noticed that HSCs require a “buddy” cell type to help them form. These “buddies,” known as endotome cells, have stem cell–inducing properties.
“Endotome cells act like a comfy sofa for pre HSCs to snuggle into, helping them progress to become fully fledged stem cells. Not only did we identify some of the cells and signals required for HSC formation, we also pinpointed the genes required for endotome formation in the first place,” Currie says.
“The really exciting thing about these results is that if we can find the signals present in the endotome cells responsible for embryonic HSC formation, then we can use them in vitro to make different blood cells on demand for all sorts of blood-related disorder.”
“Potentially it’s imaginable that you could even correct genetic defects in cells and then transplant them back into the body,” Currie says.
Source: Monash University