ABSTRACT
MHC I & II genes deleted using CRISPR Cas-9
BACKGROUND Regenerative medicine therapies using stem cells possess the capability to save millions of lives but its progress is hampered by the possibility of immune-rejection by the patient’s immune system. Universal stem cells offer a solution to this problem.
Chromosome 6 of required iPSC
RATIONALE Through this poster,it has been attempted to explain this novel concept in a concise and easy-to-understand manner.
MHC I & II
STRATEGY Traced the history of the various attempts that were made to delete specific genes affecting the immune system in iPSCs and ECSs. Drew out a flowchart of the basic process involved in generating hypoimmunogenic iPSC.
part of the immune system that presents antigens to the T-cells
RESULT Scientists have been experimenting with editing the immune components of iPSC sequentially, first modifying one and then the other component. Using this methodoogy, researchers have discovered a particular combination of edits that gives rise to an iPSC that is able to hide itself from the host's immune system therby facilitating successful long-term transplantations without the threat of rejection.
CD 47 CD 47 overexpressed
CONCLUSION
Ig that acts as "do not kill me signal" to evade Natural
Laboratory generated hypoimmunogenic iPSCs have successfully been used to replace endothelial, smooth muscle cells and cardiomcytes in immunocompetent mouse models. It is only a matter of time before we will be able to run human trials.
Killer cells
UNIVERSAL STEM CELLS
Hypoimmunogenic iPSC
Triple engineered stem cells that are "invisible to the immune system"
all MHC class I were removed by beta-2 m deletion which prevents Tc and Th attack but
non-edited iPSC
still allows NK cells
which can be
to identify. This can
targeted byÂ
be blocked by
cytotoxic T cells
upregulating CD
(Tc), helper T cells
47 expression
(Th), and NK cells
which also blocks macrophage destruction
selective deleton of HLA-A,B and D while retainng
a suicide gene would
HLA-C protected
provide the ultimate
iPSC
from Tc, Th
safety key by ensuring
and NK attacks.
a mchanism to prevent
But these were sill
tumorigenesis which is
suceptible to
assoiated with CD 47
minor
overexpression
histocompatibility antigens
-S KAREN JESSICA