We are often told that sleep is one of the most important parts of a healthy lifestyle, and that it helps heal and repair our heart and blood vessels, among other things.

It turns out that sleep, or something similar, is equally important for stem cells, helping them retain their power, or potency, a measure of their effectiveness and efficiency in generating the mature adult cells needed to repair damage. Now researchers at Stanford, with a little help from CIRM, have found a way to give stem cells the rest they need before kicking into action. This could pave the way for a whole new approach to treating a variety of genetic disorders such as muscular dystrophy.

Inside out

One problem that has slowed the development of stem cell therapies is the inability to manipulate stem cells outside the body without reducing their potency. In the body, these cells can remain quiescent or dormant for years until an injury calls them into action to repair it. That’s because they are found in a specialized environment or niche, one that has very particular physical, chemical and biological properties. However, once researchers remove stem cells from that niche and place them in a lab dish, they become active, start proliferating, and change into other kinds of cells.

You might think that’s good, because we want those stem cells to change and mature, but in this case we don’t, at least not yet. We want them to wait till we return them to the body to do their magic. Changing too soon means they have less power to do that.

Researchers at Stanford may have found a way to prevent that by creating a lab environment that more closely resembles the body, so the stem cells stay dormant longer.

As senior author Thomas Rando said in a Stanford news release, they have found a way to keep the stem cells dormant longer:

“Normally these stem cells like to cuddle right up against their native muscle fibers. When we disrupt that interaction, the cells activate, begin to divide, and become less stemlike. But now we’ve designed an artificial substrate that, to the cells, looks, smells, and feels like a real muscle fiber. When we also bathe these fibers in the appropriate factors, we find that the stem cells maintain high-potency and regenerative capacity.”

Creating an artificial home

When muscle stem cells are removed from a mouse, they lose potency within two days. The Stanford team set out to identify which elements in the niche kept these cells dormant. They mapped the molecular signature of quiescent MuSCs and used it to screen compounds that could maintain dormancy outside the mouse.

They narrowed 50 compounds to 10, then tested combinations until they found one that kept MuSCs quiescent for at least two days in culture.

Next, they tested engineered muscle fibers to mimic the niche’s physical environment. The most elastic material worked best, so they used it to create a scaffold for the stem cells.

The big test

The artificial niche kept MuSCs dormant in the lab—but would they function when transplanted back into mice? The researchers found they did. These MuSCs self‑renewed and differentiated more effectively than cells stored under standard conditions.

They then tested human muscle stem cells. hMuSCs cultured on the artificial niche also showed better self‑renewal and retained potency longer than those kept conventionally.

In their Nature Biotechnology study, the researchers say this system could help overcome barriers that have slowed progress in muscle stem cell therapies:

“Very small numbers of quiescent stem cells—even single cells—can replace large amounts of tissue. Culture systems that maintain quiescence may help translate these findings to the clinic. The ability to culture hMuSCs longer without losing potency could support gene‑correction strategies for disorders like muscular dystrophy, followed by transplantation of corrected cells.”