16 January 2015

Imaging The Process of How Blood Stem Cells Take Root

Scientists at Stem Cell Research Program of the Boston Children's Hospital has successfully imaged the process on how blood stem cells work inside the body to generate blood.

Using see-through zebrafish and genetic tagging, the scientists got a direct visualization of how the stem cells take root in the body to generate blood.

Owen Tamplin, PhD, the paper's co-first author says, "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 their blood system, but what happens in between can't be seen. Now we have a system where we can actually watch that middle step.

The steps are detailed in the video below.

This discovery can lead to new therapies and processes that can improve bone marrow transplants in patients that require it.

Stem cells are special cells in the body that can differentiate into a higher form of cells such as cell tissues and organs. There are different types of stem cells that are associated with a biological system such as heart stem cells. Pluripotent stem cells are cells that can differentiate into any type of cell regardless of origin.

Hematopoietic stem cells are stem cells that comes from the bone marrow ,umbilical cord blood, embryo, or in peripheral blood of the human body. These are the type of stem cells used to treat blood based diseases such as lymphoma and leukemia.

Live Imaging the Blood Stem Cell Process

A see-through zebrafish and enhanced imaging provide the first direct glimpse of how blood stem cells take root in the body to generate blood. Reporting online in the journal Cell today, researchers in Boston Children's Hospital's Stem Cell Research Program describe a surprisingly dynamic system that offers several clues for improving bone marrow transplants in patients with cancer, severe immune deficiencies and blood disorders, and for helping those transplants "take."

The steps are detailed in an animation narrated by senior investigator Leonard Zon, MD, director of the Stem Cell Research Program (see video below). The Cell version offers a more technical explanation

"The same process occurs during a bone marrow transplant as occurs in the body naturally," says Zon. "Our direct visualization gives us a series of steps to target, and in theory we can look for drugs that affect every step of that process."

The blood system's origins

It had already been known that blood stem cells bud off from cells in the aorta, then circulate in the body until they find a "niche" where they're prepped for their future job creating blood for the body. For the first time, the researchers reveal how this niche forms, using time-lapse imaging of naturally transparent zebrafish embryos and a genetic trick that tagged the stem cells green.

A more technical explanation of the same video can be found here: cell 160_1 + 2 PFB

On arrival in its niche (in the zebrafish, this is in the tail), the newborn blood stem cell attaches itself to the blood vessel wall. There, chemical signals prompt it to squeeze itself through the wall and into a space just outside the blood vessel.

"In that space, a lot of cells begin to interact with it," says Zon. Nearby endothelial (blood-vessel) cells wrap themselves around it: "We think that is the beginning of making a stem cell happy in its niche, like a mother cuddling a baby."

As the stem cell is being "cuddled," it's brought into contact with a nearby stromal or "nurse" cell that helps keep it attached. The stem cell hooks onto the nurse cell tightly, in a process Zon likens to early "attachment" of an infant to its mother.

The "cuddling" was reconstructed from confocal and electron microscopy images of the zebrafish taken during this stage. Through a series of image slices, the researchers were able to reassemble the whole 3D structure--stem cell, cuddling endothelial cells, and stromal cells.

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

Eventually, the cuddled stem cell begins dividing. One daughter cell leaves the niche while the other stays. Eventually, all the stem cells leave and begin colonizing their future site of blood production (in fish, this is in the kidney).

Further imaging done in mice found evidence that blood stem cells go through much the same process in mammals, which makes it likely in humans too. In humans, blood stem cells set up permanent residence in the bone marrow.

These detailed observations are already informing the Zon Lab's attempt to improve bone marrow transplantation. By doing a chemical screen in large numbers of zebrafish embryos, the researchers found that the compound lycorine promotes interaction between the blood stem cell and its niche, leading to greater numbers of blood stem cells in the adult fish


Boston Children's Hospital
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