An international research effort has found that mature animal cells can be shocked into an embryonic state simply by soaking them in acid or putting them under physical stress. The fortuitous breakthrough could prove to be massive for many fields of medical research if the method can be replicated using human cells, something researchers are confident will be possible.
The collaboration between Harvard-affiliated Brigham and Women’s Hospital (BWH) and the Riken Center for Developmental Biology in Japan found that by bathing mature cells harvested from mice in a weak acid, they reverted to a stem cell-like pluripotent state. Pluripotency, as the name suggests, is when a cell has the potential to become one of the many different cells found in an animal; "pluri" refers to many, as in plural, and "potent" – the potential to become that many.
Pluripotent cells are an important resource for many forms of medical research. Embryonic stem cells (ESCs) are one type of pluripotent cell, yet the harvesting of ESCs has its opposition, as it involves the destruction of human embryos. Successful attempts at creating stem cells culminated in the 2012 Nobel Prize-winning research in which Shinya Yamanaka produced Induced Pluripotent Stem Cells (iPSC) from mature cells by introducing several pieces of DNA. The new technique being pioneered by researchers at Harvard and Riken is much simpler and would greatly reduce the expense of stem cell production.
“It may not be necessary to create an embryo to acquire embryonic stem cells. Our research findings demonstrate that creation of an autologous pluripotent stem cell, a stem cell from an individual that has the potential to be used for a therapeutic purpose without an embryo, is possible,” said senior author Dr. Charles Vacanti, chairman of the Department of Anesthesiology, Perioperative and Pain Medicine and director of the Laboratory for Tissue Engineering and Regenerative Medicine at BWH.
The origins of the research date back to 2001 and can be credited to Dr. Vacanti, a BWH anaesthesiologist best known for his work on the “earmouse” which gained notoriety in 1995. In 2001, Dr. Vacanti was working towards finding new cell types able to be used in his tissue engineering research. During this study he mistakenly reported a new type of stem cell he called “spore-like cells," by passing neural stem cells and mature tissue cells through ever-smaller pipettes. He believed that these spore-like cells existed in all tissue, and that they remained dormant until needed to repair tissue damage. After heavy peer criticism, the research was shelved.
Six years on, enter Japanese graduate student Haruko Obokata. Armed with new insight, Dr. Vacanti and Obokata started investigating if the harsh process of extraction had produced the stem cells rather than his previous belief that they had been isolated from the tissue mixture. This new line of inquiry led the researchers to a remarkable finding, namely that any mature adult (somatic) cell has the potential to turn pluripotent if subjected to sub-lethal stress such as mild acidity, high or low temperature, or mechanical force. They named the process stimulus-triggered acquisition of pluripotency (STAP). It can be seen taking place in the following video.
Mature blood cells taken from a live donor and engineered to glow were treated with a mild acid. These decreased in size and lost their functional characteristics during the process of conversion from mature somatic cell to STAP cell. The glowing STAP cells were then introduced to a (non-glowing) mouse blastocyst and were shown to contribute 100 percent to the somatic tissue in the embryo that formed. This was easily seen, as the embryo indeed glowed.
“It’s exciting to think about the new possibilities these findings open up, not only in areas like regenerative medicine, but perhaps in the study of cellular senescence and cancer as well. But the greatest challenge for me going forward will be to dig deeper into the underlying mechanisms, so that we can gain a deeper understanding of how differentiated cells can covert to such an extraordinarily pluripotent state,” Obokata said.
The research was published in the journal Nature. The glowing mouse embryo can be seen in the video below.