University of California researchers have been focused on genetically engineering pluripotent stem cells that can bypass the body’s immune response and thus preempt rejection. To bypass the issue of donated tissues stem cells have been created out of mature fully developed cells that have been collect from the patients to be modified and then readministered. These iPSCs are hoped to help minimize chances of rejection, and to later specialize as they step into their new roles if the immune system does not attack them as a potential pathogen.
As promising as it is even this route has obstacles, and even these cells engineered from the patient’s own cells still face rejection; moreover the process is costly and can be difficult to conduct, and harder still to reproduce successful attempts. According to Dr. Tobias Deuse there are many issues with iPSc technology such as not knowing what makes some cells reliably reprogrammable; and most individualized iPSC therapies have been abandoned due to it.
Scientist believe they may have found a solution by taking an approach that creates a new universal pluripotent stem cell, which can differentiate into any specialized cell without triggering an immune response, and without the need to administer immune suppressing drugs that can leave patients more susceptible to cancer and infection.
To overcome these obstacles CRISPR-Cas9 gene editing was used to modify activity of as little as 3 genes to shield the stem cells from immune response and allow the body to accept them more easily. The altered stem cells were tested in mouse models with fully functioning immune systems designed to resemble histocompatibility mismatch.
The stem cell engineering process was started by deleting two genes that control activity of histocompatibility complex class I and II proteins that send out signals to the immune system and trigger immune responses. However the cells did not get a free pass, they then became targeted by specialized natural killer immune cells. CD47 a cell surface protein was found to inhibit these NK cells in laboratory and in vivo studies.
New engineered stem cells with 2 muted and one enhanced gene were transplanted into specially engineered mice that had immune system elements to stimulate immune responses in humans, experiments were reported to be successful.
Going one step further these new stem cells were then coaxed to specialize as different types of heart cells, which were once more transplanted into specially engineered mice; these studies were also reported as being successful as the new heart cells survived for a long time, along with forming into simple blood vessels and heart muscle tissues.
Dr. Deuse emphasizes based on their finding the team suggests that such stem cells can eventually be used to treat humans; and the technique solves rejection problems which represents a significant advance for the field of stem cell therapy.
