A Bit of Stress Yields Stem-Cell Surprise; New Way of Forming Stem Cells From Specialized Cells Could Be Safer, More Ethical

A Bit of Stress Yields Stem-Cell Surprise

New Way of Forming Stem Cells From Specialized Cells Could Be Safer, More Ethical

GAUTAM NAIK 

Updated Jan. 29, 2014 5:55 p.m. ET

Researchers have transformed specialized cells into an embryonic-like state simply by stressing them out a bit—an unexpected finding that may one day offer an easier route for treating diseases with patient-specific stem cells.

For clinical use, stem cells that can become all other tissue types would potentially be obtained in two ways. One way would require a patient’s cells to be cloned into an embryo in a lab dish; extracting stem cells from such an embryo is controversial because it is destroyed in the process. The second potential approach, which uses genes to reprogram a patient’s mature cells into an embryonic-like state, carries the risk of cancer.

Now, in a series of experiments done over five years, scientists have shown that merely exposing blood cells from newborn mice to a low-acid environment—the source of stress—also changes them to an embryonic-like state. The key advantage is that no potentially risky genetic manipulation is needed.

“It was really surprising to see that such a remarkable transformation could be triggered… from outside the cell,” said Haruko Obokata of the Riken Center for Development Biology in Kobe, Japan, and lead author of two separate studies published Wednesday in the journal Nature.

Any benefits for medicine are years away. It still needs to be shown that the approach works with human cells. It must also work on mature cells from adult patients, not just newborns. Nonetheless, the findings could spark further studies in the same vein in labs around the world.

Specialized cells usually need to remain specialized cells. If heart cells suddenly became liver cells or vice versa, biological chaos would ensue.

However, in some plants, amphibians, birds and reptiles, mature cells can switch identity. In rare cases, it can be triggered by the environment. A crocodile embryo will turn into a male or a female depending on the temperature during incubation. But scientists always have believed that mammalian cells are resistant to such changes.

The latest experiments, chronicled in Nature, indicate that may not be the case.

Dr. Obokata said she initially subjected white blood cells from newborn mice to various stresses in a lab dish. One worked especially well: In the presence of a solution with low acidity, a small proportion of cells lost their “blood cell” identities and became “pluripotent”—the key property of embryonic cells, which allows them to become almost all other tissues in the body.

The researchers dubbed this transformation stimulus-triggered acquisition of pluripotency, or STAP. When the STAP cells were injected into embryos, they gave rise to chimera mice that had cells from both the host embryo and the STAP cells. It suggested that lab-made STAP cells were biologically viable.

With further tweaking, it was shown that STAP cells could divide and renew over a long period, just like true embryonic stem cells.

The biggest surprise was yet to come. Charles Vacanti, a tissue engineer at Harvard Medical School and Brigham and Women’s Hospital and co-author of both Nature papers, notes that depending on the chemical environment in which the STAP cells were placed, they could be turned into either placenta cells or embryonic stem cells.

“To my mind that makes them totipotent,” said Dr. Vacanti, whose research over the past 15 years laid the groundwork for the latest findings. Totipotency is the ability of a cell to give rise not just to the embryo but also the placenta. If confirmed, that would be a scientifically intriguing result because the only totipotent mammalian cell is a fertilized egg.

Dr. Vacanti’s team has done two more intriguing experiments, both unpublished so far. One was to assess whether the technique works with human cells. Differentiated cells from the foreskins of human newborns were subjected to mechanical stress, which injured the cell walls. That appeared to convert them to what looks a lot like STAP cells. Further tests will confirm whether they are the real thing.

Dr. Vacanti has also implanted STAP cells into a handful of monkeys suffering from spinal-cord injury. He says the results were “very impressive” but still need to be validated.