Researchers have successfully treated sickle-cell anemia in mice by using stem-cell

Healthy blood cells can be made to replace sickle-cells by transplanted stem cells.


Stem cells treat anaemia in mice

Results provide proof of principle for therapeutic promise of induced pluripotent stem cells.

Researchers have successfully treated sickle-cell anemia in mice by using stem-cell lines created from cells at the tip of a mouse tail. It is the first demonstration that ‘induced pluripotent stem cells’ — adult cells that have been reprogrammed to behave more like embryonic stem cells — can be used therapeutically.

The work is a critical step towards establishing whether these cells could one day lead to therapies derived from an individual’s own tissue, eliminating the risk of rejection by the immune system. But researchers are quick to caution that there is still much to be done before the cells are ready for human trials.

"It demonstrates a very important, pre-clinical proof of principle," says George Daley, a stem-cell researcher at Children’s Hospital Boston in Massachusetts, who was not an author on the study. “But it also highlights that many, many questions linger about the safety of these cells.”

More than five years ago, Daley and Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, used therapeutic cloning to create embryonic stem cells capable of correcting a genetic immune deficiency1. But that method was technically challenging and, for some, ethically worrisome because of its use of embryos.

Since then, researchers have learned how to reprogramme mouse and human adult cells to behave more like embryonic stem cells. The resulting cells, called induced pluripotent stem cells, are able to differentiate into many different cell types. But their therapeutic potential had not yet been established. Researchers have been clamouring to try out the new cells on their favourite disease models.

Model disease
Jaenisch decided to use the cells to tackle sickle-cell anaemia because the genetic basis of the disease is well understood and the mouse models closely mimics the human disease. So Jaenisch, along with Tim Townes of the University of Alabama at Birmingham and their colleagues, generated induced pluripotent stem cells from a mouse with a sickle-cell mutation in one of its globin genes.

The team then engineered the induced pluripotent stem cells to become healthy blood-producing cells, by replacing the defective globin gene with a normal copy. The stem cells were then transplanted back into three genetically identical sick mice, which had been irradiated to destroy their faulty blood-producing cells.

Twelve weeks after the procedure, mice treated with the engineered stem cells had more normal blood, including higher red-blood-cell counts and hemoglobin content, than untreated sickle-cell mice. The results are published this week in Science 2.

Weighing the risks
Transplantation of induced pluripotent stem cells can carry a high cancer risk. The researchers lowered this risk by not using one particular cell reprogramming ingredient: a cancer-causing protein called c-Myc. Three months after the transplant, there was still no sign of tumours in these mice. But that doesn’t mean that tumours won’t show up eventually, cautions Jaenisch.
Researchers won’t really know how well these cells stack up against adult stem cells or embryonic stem cells until they are directly compared, says Evan Snyder, a director at the Burnham Institute for Medical Research in La Jolla, California. “Ultimately one really needs to do this with all the various flavours of stem cells out there,” says Snyder. “One needs to compare them head-to-head, and let the data dictate which is the safest and which is the most efficacious."

It may be that different diseases will be best treated by using different kinds of stem cells, or even combinations of stem cells. “It’s just like an artist who has a really wide palette of colours,” says Snyder. “To give you a beautiful picture, we want to be free to dabble in all the colours.”