Before blood stem cells can mature, before they can grow and multiply into the red blood cells that feed our organs, or the white blood cells that protect us from pathogens, they must go on a journey.

A blood stem cell en route to taking root in a zebrafish. [Credit:
Boston Children’s Hospital]

This journey, which takes place in the developing embryo, moves blood stem cells from their place of origin to where they will take root to grow and mature. That this journey happened was well known to scientists, but precisely how it happened remained shrouded in darkness.

But now, for the first time, scientists at Boston Children’s Hospital have literally shone a light on the entire process. In so doing, they have opened the door to improving surgical procedures that also rely on the movement of blood cells—such as bone marrow transplants, which are in essence stem cell transplants.

Reporting in today’s issue of the journal Cell, Boston Children’s senior investigator Leonard Zon and his team developed a way to visually track the trip that blood stem cells take in the developing embryo. As described in today’s news release, the same process that guides blood stem cells to the right place also occurs during a bone marrow transplant. The similarities between the two, therefore, could lead to more successful bone marrow transplants. According to the study’s co-first author Owen Tamplin:

“Stem cell and bone marrow transplants are still very much a black box—cells are introduced into a patient and later on we can measure recovery of the blood system, but what happens in between can’t be seen. Now we have a system where we can actually watch that middle step.”

And in the following video, Zon describes exactly how they did it:

As outlined in the above video, Zon and his team developed a transparent version of the zebrafish, a tiny model organism that is often used by scientists to study embryonic development. They then labeled blood stem cells in this transparent fish with a special fluorescent dye, so that the cells glowed green. And finally, with the help of both confocal and electron microscopy, they sat back and watched the blood stem cell take root in what’s called its niche—in beautiful Technicolor.

“Nobody’s ever visualized live how a stem cell interacts with its niche,” explained Zon. “This is the first time we get a very high-resolution view of the process.”

Further experiments found that the process in zebrafish closely resembled the process in mice—an indication that the same basic system could exist for humans.

With that possibility in mind, Zon and his team already have a lead on a way to improve the success of human bone marrow transplants. In chemical screening experiments, the team identified a chemical compound called lycorine that boosts the interaction between the zebrafish blood stem cell and its niche—thus promoting the number of blood stem cells as the embryo matures.

Does the lycorine compound (or an equivalent) exist to boost blood stem cells in mice? Or even in humans? That remains to be seen. But with the help of the imaging technology used by Zon and the Boston Children’s team—they have a good chance of being able to see it.