A new study demonstrates how patient-derived stem cells might one day be used to treat genetic diseases. Scientists from Cambridge, England, corrected a genetic error in stem cells derived from patients with a liver disease, and then differentiated them into liver cells. When injected into the livers of mice, the cells integrated into the organ and started functioning normally.
“They showed that the cells are able to function; that’s a very big achievement and a great opportunity,” says Anil Dhawan, a researcher at King’s College London who was not involved in the study. The study was published today in Nature.
The research combines several techniques, including cell reprogramming and gene editing, that scientists hope will make gene therapy and cell replacement therapies a reality. While safety testing is needed before the treatment can be tested in people, researchers used technologies that left the cells “pristine,” with no signs of the genetic manipulation that took place. This makes them more likely to be suitable for patients.
Researchers first collected cells from patients with α1-antitrypsin deficiency, an inherited disease that strikes one in 2,000 people of northern European descent. People with the disease have a single letter mutation in both copies of the α1-antitrypsin gene. The mutated protein builds up in liver cells, killing off the tissue and eventually necessitating a liver transplant.
Organs for transplant are scarce, so Allan Bradley, a geneticist at the Wellcome Trust Sanger Institute, and collaborators set out to create a new source of replacement tissue. “The liver is a good place to do cell correction therapy because it is a relatively simple organ compared to the brain, lung, or heart,” he says. “It will regenerate to the same size and shape of the original.”
Bradley’s team transformed the adult cells into stem cells using a technique called induced pluripotent stem (iPS) cell reprogramming, in which scientists use a cocktail of genetic factors to turn back the cells’ developmental clock. The resulting cells can both grow more of themselves and can differentiate into any type of tissue.
The benefit of iPS cells is that they are genetically matched to the donor, meaning they can be transplanted back into the patient without triggering an immune attack. (People who receive organ or cell transplants must take immunosuppressive drugs to stop the body from attacking the foreign tissue.)