Many of us know by now that stem cells are remarkably fluid in the types of cells they can become. But this fluidity, or pluripotency, comes with a price. Several studies have shown that the body's immune system will attack and reject even genetically identical transplanted stem cells, making it difficult to envision their usefulness for long-term therapies.
Now Stanford cardiologist Joseph Wu, MD, PhD, and his colleagues have shown that coaxing the stem cells to become more-specialized (a process known as differentiation) before transplantation allows the body to recognize and tolerate the cells. Their research was published today in Nature Communications (subscription required).
From our release:
In a world teeming with microbial threats, the immune system is a necessary watchdog. Immune cells patrol the body looking not just for foreign invaders, but also for diseased or cancerous cells to eradicate. The researchers speculate that the act of reprogramming adult cells to pluripotency may induce the expression of cell-surface molecules the immune system has not seen since the animal (or person) was an early embryo. These molecules, or antigens, could look foreign to the immune system of a mature organism.
Previous studies have suggested that differentiation of iPS cells could reduce their tendency to inflame the immune system after transplantation, but this study is the first to closely examine, at the molecular and cellular level, why that might be the case.
Postdoctoral scholars Patricia Almeida, PhD, and Nigel Kooreman, MD, and assistant professor of medicine Everett Meyer, MD, PhD, share lead authorship of the study. They found that laboratory mice accepted grafts of endothelial cells made from stem cells much more readily than they did the stem cells themselves. As Wu, who also directs the Stanford Cardiovascular Institute said in our release:
This study certainly makes us optimistic that differentiation — into any nonpluripotent cell type — will render iPS cells less recognizable to the immune system. We have more confidence that we can move toward clinical use of these cells in humans with less concern than we’ve previously had.
Previously: New technique prevents immune-system rejection of embryonic stem cells and Overcoming immune response to stem cells essential for therapies, say Stanford researchers
Photo by Umberto Salvagnin