It is essential to give us the key to leukemia

The bone marrow is undoubtedly one of the most complex, and at the same time vital, tissues in the human body. It can be said that it is the “blood factory” of the body where stem cells are born that keep us alive and that gives rise to our defenses or our red blood cells. However, studying it is a real nightmare as it is encapsulated within the bone such as the femur.

Until now, scientists had to choose between study cells on a flat piece of plastic (which looks nothing like the real body) or use micewhich, spoiler: they are not human. That is why there is now a real revolution in this field, since they have managed to create a great model that will make life much easier for science.

The study published in Stem Cell just changed the rules of the game. A team of researchers have managed to create eVON, a macroscale, 3D, vascularized model of the human bone marrow that not only has cells, but “breathes”, has functioning blood vessels and even nerves.

Why does it matter? Although it seems insignificant, the reality is that right now there were many doubts about how they develop diseases as aggressive as leukemia. In this case, this piece of tissue engineering opens the door to finally understanding how leukemia works and how to cure it without depending so much on animal models that are not faithful to the anatomy and physiology of humans.

Until now, the solution to research also involved taking a Petri dish, which is nothing more than a piece of plastic, and cultivating the stem cells here that will give rise to the components that we have in our blood. Logically, they died quickly here, since they lacked the environment where they were truly comfortable ‘living’. It is what is known as endosteal niche.

This niche is the specific neighborhood within the bone where stem cells interact with blood vessels, bone, and nerves to decide whether to multiply or become white or red blood cells. Something fundamental to understand what is happening there.

We already have a solution. eVON is presented as a wonderful alternative, since it has three key elements:

• A ‘scaffold’ composed of the same mineral that we have in bone to imitate the hard structure of the trabecular bone human. No white gelatin, but something that feels like a real bone.
• Stem cells that have been reprogrammed in the laboratory to generate both bone and blood tissue.
• Functional vascularization, thanks to the fact that they have managed to make the cells form networks of capillaries and blood vessels that penetrate the artificial bone. And the truth is that they have managed to introduce all the components that are around them into our marrow.

Most surprising is the level of detail: The model spontaneously developed sympathetic nervous system nerve fibers and macrophage-like cells, creating an entire ecosystem that no one had ever had to explicitly “design” cell by cell. They have literally created a blood factory.

The fight against leukemia. Acute myeloid leukemia is a cancer that is undoubtedly devastating and that often “hides” in the bones themselves, making it very resistant to chemotherapy since it is difficult for the medication to reach the bones. The good news comes when the study shows that eVON recreates the exact molecular signals that tumor cells use to survive.

And this is fundamental, since attacking these genes is like hitting their weak point. In short, it gives us the necessary tools to be able to kill tumor cells and cause them to die.

The test. To prove that their “artificial bone” was robust, the researchers did something worthy of science fiction: they implanted the eVON tissue under the skin of mice.

And the truth is that the result was very good: the human tissue integrated with the mouse and the human blood vessels connected with those of the mouse. In this way, the human stem cells survived and were able to repopulate the mouse blood with functional human cells.

But logically there are still challenges that must be overcome, such as the size of this model. To do this, it still needs to be reduced so that large-scale tests can be carried out with drugs that can kill these tumor cells.

Images | ANIRUDH National Cancer Institute

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