these problems, scientists at the University of California, San Francisco have
can be safely used for transplants without being attacked by the body's immune
This neat bit
of biogenetic engineering in lab studies has made pluripotent stem cells
which are functionally 'invisible'
immune system thereby eliminating the risk of immune system attacks and
Gene Editing and Stem
Deuse, MD, Endowed Chair of Cardiac Surgery at UCSF, said that while pluripotent stem cells have immense potential to grow into any
adult tissue there is always the risk of the immune system mounting an attack.
The immune system is programmed to reject anybody it considers alien be it a
new organ, tissues or cells. This mounting attack leads to the rejection
of transplants. This is known as histocompatibility mismatch
donor and recipient.
Dr. Sonja Schrepfer,
MD, senior director of this study and director of the UCSF Transplant and Stem
Cell Immunobiology (TSI) Lab says that though immunosuppressants are given to
patients to avoid rejection, this class of drugs makes the patient more prone
to cancer and other serious infections.
Dr. Deuce and
Dr. Schrepfer were able to surmount these challenges and went on to create 'universal' iPSCs
by changing the activity of three major genes responsible for
histocompatibility mismatch. This means these iPSCs can be safely
transplanted even in histocompatibility mismatched recipients without being
The team used
to delete two genes which supervise the functioning of a family of proteins
called major histocompatibility complex (MHC) class I and II. MHC proteins
usually sit on the surface of the cells and send out molecular signals to
enable the immune system to recognize alien cells.
do not have the MHC genes do not give out such signals since the immune system
no longer recognizes it as alien. However, cells without MHC genes become the
target of immune cells called natural killer (NK) cells.
Breakthrough in Stem Cell Therapy Field
collaborated with Prof. Lewis Lanier, co-author of the study and chairperson of
the Department of Microbiology and Immunology who is an expert NK cell activity
and signaling. The team found that CD47 which is a cell-surface protein signals
a 'Do not kill me' message
macrophages which in turn influence NK cell activity.
Next the team
used a viral vector to insert the CD47 gene copies which were then delivered to
mouse and human stem cell lines which had the missing MHC proteins. As
expected, this was the turning point. After transplanting the bioengineered
mouse stem cells into mismatched mice with strong immune systems, no rejection
The research team
also created different types of human heart cells from triple bioengineered
stem cells which were again transplanted into mice. The stem cell-derived
cardiac cells were able to survive much longer and started forming basic blood
cells and heart muscle cells. This raises the hope of using these techniques to
repair failing human hearts.
technique is a major breakthrough in the stem cell therapy field and
can be successfully used for cell, tissue and organ
transplantation minus the risks of rejection.
- Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients - (https://doi.org/10.1038/s41587-019-0016-3)
- CRISPR Gene Editing Makes Stem Cells 'Invisible' to Immune System - (https://www.ucsf.edu/news/2019/02/413311/crispr-gene-editing-makes-stem-cells-invisible-immune-system)