The Change of HEART
Tissue hypoxia, or ischemia, is the condition that describes the poor conveyance of oxygen and
other vital products to body tissues and organs which consequently results tissue death.
Up to now,the number one cause of death worldwide is caused by ischemia and related conditions such as
heart attack or stroke. Additionally, due to the remarkable damage to tissues, these diseases end
up with high morbidity rates. From pharmacology to biomedical industry, variety of prevention and
treatment options have been suggested, many of them have still being applied. Nevertheless, we
still have not reached the very end of cure and more novel approaches from different fields may play
great role for this reason. One of these approaches is, of course, synthetic biology. The benefits of
SynBio allow us to manipulate micro and nano scales of cell environment in order to involve in when
the action starts and to interfere at the right time.
Ischemic damage is related with two different phenomena. First, the vital blood supply that carry
oxygen, energy gathering nutrition and other minerals is cut down by an external effect, mostly by
a clot. Afterwards, cells become unable to produce enough energy and start wasting their deployed
nutrition in a different reaction cascade that results with building up toxic chemicals in the media.
If the clot barrier is removed, excessive oxygen presence in the media may enhance this toxic
production because of high metabolic rate of the cells. These toxic products, also known as reactive
oxygen species (ROS), may increase the cell damage further. Thus, it is needed to regard the big
picture of the condition In order to solve the problem.
In our project, our will is to build two different devices, which work synergistically, to fix these two
distinct situations. To do this, we aim to design hypoxia inducible systems, which is the first step for
constructing a sensitive and robust device. Hypoxia inducible promoters and their regulator proteins
are responsible for this critical mission. Beside of this, we also want to prevent the damage caused
by reperfusion of blood to the hypoxic environment, we also need an additional sensitive receptor
construct. After our researches, we decided to use reactive oxygen species (ROS) sensitive promoter
systems. These two receptors will hopefully regulate the release of clot dissolving factors synthesized
by our engineered vessel cells. Moreover, we hope to maximize the reduction of ROS damage to the
cells by producing antioxidant enzymes to degrade ROS within the cells. By re-providing vital oxygen
support via bloodstream and enhancing the degradation of ROS in the tissue, this project intends to
propose a new treatment approach for ischemia related diseases.
In the future, following the advancements in gene therapy and cell therapy industries, we would
like to implement our system in living models. Especially, tissue engineered heart vessel cells or
manipulating the whole body by gene containing exosomes, this treatment option may also pose an
alternative prevention method for ischemic heart attack or strokes.
We hope to bring encouraging
results in vitro to pave the way of this promising system into the lifesaving remedy method.
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