Stem cell discovery could improve treatments for leukemia, other diseases

The inability to get human blood stem cells, or hematopoietic stem cells (HSCs), to self-renew in the laboratory is holding back progress in treating leukemia and other blood diseases.

Now, a new study from the University of California, Los Angeles (UCLA) suggests that the answer may lie in a particular protein — the activation of which can greatly expand HSCs in culture.

The UCLA team found that a protein called MLLT3 is a key regulator of HSC function. The protein is present at high levels in the HSCs of human fetuses, newborns, and adults. However, cultured HSCs have low levels of MLLT3.

In a recent Nature paper, the researchers report how manipulating the gene responsible for making the protein led to a "more than 12-fold expansion of transplantable" HSCs.

The senior author of the study paper is Hanna K. A. Mikkola, a professor of molecular, cell, and developmental biology at UCLA. She has been studying HSCs for more than 20 years.

"Although we've learned a lot about the biology of these cells over the years," says Mikkola, "one key challenge has remained: making [HSCs] self-renew in the lab."

"We have to overcome this obstacle to move the field forward," she adds.

HSCs need powerful ability to self-replicate

All tissues and cells of the body rely on blood cells for nourishment and protection. To fulfill such a relentless and onerous task, blood cells must be able to replenish themselves. In adults, blood cells and skin cells have the greatest replenishment capacity of any tissue.

The job of making new blood cells falls to HSCs. Every day, the human body makes billions of new blood cells, thanks to HSCs, which also make immune cells.

HSCs reside in bone marrow, where they self-renew and mature into different types of blood and immune cells.

People with certain diseases of the blood or immune system — such as leukemia — need fresh supplies of HSCs to make new cells. For decades, doctors have used bone marrow transplants to boost their supplies.

However, there are limits on the extent to which bone marrow transplants can offer a solution. For instance, it is not always possible to find a matching donor, or the recipient's body might reject the transplanted cells.

Another problem that can arise is that the number of transplanted HSCs may not be enough to generate sufficient blood or immune cells to treat the disease.

The problem with cultured HSCs

Scientists have tried to culture HSCs in the laboratory as an alternative to bone marrow transplants. However, various attempts to transplant cultured HSCs have hit a common problem: HSCs that scientists have removed from bone marrow soon lose their capacity for self-renewal in culture.

Once HSCs lose the ability to make new copies of themselves, the only future that they have is either to differentiate into specialized cells or to die.

Source: Medical News Today