Doctoral student finds alternative cell option for organs-on-chips


Date:
December 10, 2021
Source:
Texas A&M University
Summary:
Organ-on-a-chip technology has provided a push to discover
new drugs for a variety of rare and ignored diseases for which
current models either don't exist or lack precision. In particular,
these platforms can include the cells of a patient, resulting in
patient-specific discovery.



FULL STORY ========================================================================== Organ-on-a-chip technology has provided a push to discover new drugs for
a variety of rare and ignored diseases for which current models either
don't exist or lack precision. In particular, these platforms can include
the cells of a patient, thus resulting in patient-specific discovery.


==========================================================================
As an example, even though sickle cell disease was first described in
the early 1900s, the range of severity in the disease causes challenges
when trying to treat patients. Since this disease is most prevalent
among economically poor and underrepresented minorities, there has been
a general lack of stimulus to discover new treatment strategies due
to socioeconomic inequity, making it one of the most serious orphan
conditions globally.

Tanmay Mathur, doctoral student in Dr. Abhishek Jain's lab in the
Department of Biomedical Engineering at Texas A&M University, is
developing personalized blood vessels to improve knowledge and derive treatments against the vascular dysfunction seen in sickle cell disease
and other rare diseases of the blood and vessels.

Current cells used in blood vessel models use induced pluripotent
stem cells (IPSCs), which are derived from a patient's endothelial
cells. However, Mathur said these cells have limitations -- they expire
quickly and can't be stored for long periods of time.

Mathur's research offers an alternative -- blood outgrowth endothelial
cells (BOECs), which can be isolated from a patient's blood. All that
is needed is 50 to 100 milliliters of blood.

"The equipment and the reagents involved are also very cheap and available
in most clinical settings," Mathur said. "These cells are progenitor endothelial cells, meaning they have high proliferation, so if you keep
giving them the food they want, within a month, we will have enough
cells so that we can successfully keep on subculturing them forever."
However, the question is do BOECs work like IPSCs in the context of
organ-on- chips, a microdevice that allows researchers to create these
blood vessel models. That's a question Mathur recently answered in a
paper published in the Journal of the American Heart Association.



==========================================================================
"By combining the analytics of our vessel-chip with next-generation
RNA sequencing, I was able to show that BOECs do not differ in any
statistical way compared to the other cells," Mathur said. "Not only
can you do patient- specific studies with BOECs, you can also use these
cells as alternatives to existing cells, because at the end of the day
they are still primarily human cells. If there is a way for you to get patient-derived cells with the least effort possible, that's always
the best way to move forward." Mathur's next step is to begin testing
a larger cohort of blood samples with sickle cell disease and bring
computation into the project through machine learning and artificial intelligence. By developing a chip model that can predict variables such
as clotting time, inflammation and more, the algorithm can relate each patient's history and treatment to their disease status.

"Say I made a model on 100 patients," Mathur said. "If you give me the
101st patient and I run the same methodology for those cells, my algorithm should be able to predict if that patient is a severe, moderate or mild
sickle cell patient. It's of importance because the clinician wants
to know what is the most effective short-term and long-term treatment strategies for the patient." "Tanmay's work lays a foundation for what
lies in the future of tissue engineering and organ-on-chip technology
and the positive impact that these platforms can make in personalized medicine," Jain said.

Developing this algorithm will help reduce the guesswork clinicians have
to do in creating treatment plans.

"Right now, we do not know how much of a drug to give to a mild
patient. That's why we overcorrect or undercorrect for complications,"
Mathur said. "Every drug will have certain side reactions, which you
can only minimize. The best way to minimize is to tailor your therapy
for each patient. I'm trying to minimize this iteration and minimize
the cost as well as maximize the success of the therapy for the patient." ========================================================================== Story Source: Materials provided by Texas_A&M_University. Original written
by Jennifer Reiley. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Tanmay Mathur, James J. Tronolone, Abhishek Jain. Comparative
Analysis of
Blood‐Derived Endothelial Cells for
Designing Next‐Generation Personalized
Organ‐on‐Chips. Journal of the American Heart
Association, 2021; 10 (22) DOI: 10.1161/JAHA.121.022795 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211210103054.htm

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