“Universal” iPS cells to bypass graft rejection



Researchers at the University of California, San Francisco (UCSF) used CRISPR-Cas9 to create induced pluripotent stem cells (iPSC) which are “invisible” to the immune system, thus preventing the potential for transplant rejection. These "universal" stem cells could be manufactured on a large scale more easily than "tailor-made” iPS cells designed for each patient.

 

While iPS cells have a widely accepted therapeutic potential, the immune rejection of these cells in patients receiving them is a major obstacle to their use. The use of immunosuppressants to counter immune activity may be effective, but such treatments have many side effects and make the patient more susceptible to infection and cancer. The researchers thought it would be possible to solve this transplant rejection problem using iPS cells obtained from the patient's adult cells, but in practice the clinical use of iPS has proven difficult. The quality and reproducibility of "iPS technology" is a critical point for laboratories. Additionally, the production of "customized" iPS for each patient is time consuming and expensive.

 

In response to these issues, Tobias Deuse, author of the study, and Sonja Schrepfer have created "universal iPSCs", which can be used for all patients. In their study published on 18 February by Nature Biotechnology, they describe their protocol, which includes modifying the activity of three genes to prevent graft rejection; two are related to the functioning of the major histocompatibility complex and the third protects cells from destruction by natural killer immune cells. For the first two they used CRISPR and for the third they used a virus providing a copy of the CD47 gene.

 

When researchers transplanted their mouse stem cells into HLA-incompatible mice with normal immune systems, they found no rejection. They then transplanted human iPS cells in the same way into humanized mice (whose immune systems have been replaced by components of the human immune system), and did not observe any rejection. They have also successfully derived these human iPSCs in cardiac cells and transplanted them into humanized mice.

 

"This is the first time anyone has engineered cells that can be universally transplanted and can survive in immunocompetent recipients without eliciting an immune response", the authors excitedly declared. "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, in the hope that many teams will benefit from their discovery.


Sources: 

Medical press (18/02/2019)