A new scientific discovery using gene-edited stem cells provides further evidence that scientists don’t need to kill embryos to find cures for degenerative diseases.
Researchers at the University of California, San Francisco (UCSF), announced this week they used the CRISPR gene-editing system to create stem cells that can develop into any kind of cell in the body and functionally hide from the immune system, making them rejection-proof when transplanted. The discovery could ultimately provide an ethical and efficient means of creating insulin cells for diabetes patients, heart cells for heart attack victims, neurons for stroke victims, and other replacement cells for patients with a wide range of diseases. The scientists published the findings in the journal Nature Biotechnology on Monday.
For years, scientists pushed the idea that research on embryos was essential to regenerative medicine because embryos contain pluripotent stem cells that can develop into any type of cell in the body. But the process of harvesting the stem cells destroys the embryos and ends a nascent human life. In 2007, two scientists, one from Great Britain and another from Japan, reported they had induced adult cells to become pluripotent, a discovery that does not endanger embryos. The scientists, John Gurdon and Shinya Yamanaka, won a Nobel Prize in 2012 for their discovery of the so-called induced pluripotent stem cells (iPSCs).
The latest discovery at UCSF overcomes one of the final major impediments to ethical regenerative therapy from stem cells: immune system rejection. Rejection is a potential problem with embryonic stem cell therapy because the embryos from which the cells are harvested don’t share the same DNA as the patient. (Some scientists have proposed using cloned embryos to yield genetically identical stem cells for recipients, piling on even more ethical problems.)
The UCSF scientists used gene editing to delete two genes that help with sending signals from the cell to the immune system, identifying a cell as native or foreign. They also engineered the iPSCs with a protein that acts as a “do not eat me” signal to killer immune system cells.
The scientists transplanted the resulting stem cells into mice with normal immune systems and mice with immune systems artificially changed to mimic humans’, both without any symptoms of rejection. They then derived human heart cells from the immune-blocking iPSCs and transplanted them into the humanized mice. The heart cells survived and even started forming rudimentary blood vessels and heart muscles.
“Our technique solves the problem of rejection of stem cells and stem cell-derived tissues, and represents a major advance for the stem cell therapy field,” said Tobias Deuse, the chair of cardiac surgery at UCSF and the lead author of the new study. “We only need to manufacture our cells one time and we’re left with a product that can be applied universally.”
Up until now, researchers have used an individualized approach that takes fully mature human skin or fat cells from a patient and reprograms them into iPSCs. The theory has been that cells from a patient’s own body will carry his or her DNA signature and prevent rejection. But it hasn’t worked out that well in practice: Some patients’ cells resist reprogramming, and it has proved expensive and time-consuming to produce tailor-made iPSCs for every patient. The new development could provide a reliable source of iPSCs for all patients without destroying embryos or triggering immune system rejection.
“Bottom line: it’s a big deal if it can be transferred over to the clinic,” David Prentice, a biochemist and the vice president and research director at the Charlotte Lozier Institute, told me. The development of iPSCs has already shown that medicine does not need to rely on the destruction of young human beings to get pluripotent stem cells, Prentice said. The UCSF study “pushes back big time” and means there would be “no need whatsoever for an embryonic stem cell because these cells will do anything an embryonic stem cell can do.”
Asked about the timeline for this kind of groundbreaking treatment, Prentice said he would bet scientists will try it in a clinical trial in the next two years.