Stem Cell-Based Tissue Engineered Vascular Graft

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Disclaimer — This paper partially fulfills a writing requirement for first year (freshman) engineering students at the University
of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is based on
publicly available information and may not be provide complete analyses of all relevant data. If this paper is used for any
purpose other than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at
the University of Pittsburgh Swanson School of Engineering, the user does so at his or her own risk.
STEM CELL-BASED TISSUE ENGINEERED VASCULAR GRAFT
Abigail Snyder, ams528@pitt.edu, Mahboobin 10:00, Zachary Mattis, zmm15@pitt.edu, Mahboobin 10:00
Revised Proposal — Tissue engineered vascular grafts are an
innovation that demonstrates cutting-edge stem cell
technology by utilizing the patient’s own personal
mesenchymal cells in order to grow a suitable vascular graft.
This graft can be incorporated into a patient's circulatory
system to mimic the vasoreactivity and biomechanics of the
native vasculature, while maintaining long-term patency
within the patient [1].The great leaps in the field of cellular
research has allowed for the development of new and
improved techniques to develop the tissue engineered
vascular graft (TEVG). The process to construct the TEVG
begins by extracting the mesenchymal cells from the patient.
These cells are then seeded onto a polymer scaffolding that
will serve as the original structure for the graft. After several
months of allowing the cells to multiply and grow, the graft is
then surgically implanted in place of a diseased artery. The
graft continues to grow in vivo until it is a functioning, living
tissue that can grow and remodel along with the rest of the
body. Research for the TEVG is rapidly progressing due to
the dire need for the innovation in clinical use. As stated in
the World Journal of Surgery, “Cardiovascular disease,
including coronary artery and peripheral vascular
pathologies, is the leading cause of mortality in the United
States and Western countries” [2]. The demand for a suitable
graft during bypass surgeries and other vascular
reconstructive surgeries is very high in an effort to try and
reduce the number of deaths each year due to cardiovascular
disease. Current grafting choices all include options that
require multiple follow-up surgeries to replace the old graft
used in pervious procedures. In children who need a vascular
conduit during pediatric congenital heart surgery, their
condition means a lifetime of being in and out of hospitals.
However, this TEVG has the ability to “produce tissues that
can grow, remodel, rebuild, and respond to injury” [3]
making it better than all the other current options. This new
innovation is a necessary advancement that when fully
developed has the ability to help improve the lives of
thousands of people and potentially save just as many lives.
Our plan moving forward is to specifically look for
research articles that discuss the different procedural aspects
of this technology such as the different types of cells used to
seed the scaffolding, as well as different types of biomaterials
that can be used to form the biodegradable scaffolding. We
plan on beginning our paper by explaining the development
and process of making the TEVG, followed by a discussion on
University of Pittsburgh Swanson School of Engineering 1
2016/01/29
the other current options for a vascular graft currently in use.
Additionally, we are very interested in the potential that this
type of technology has on other aspects of the medical
community, such as the different types of diseases and
medical conditions that could utilize the TEVG. There are
many medical journal articles that can be used to look into
these matters. We plan on finishing the paper with the societal
implications and benefits of this innovation to the public. In
order to gain first-hand knowledge of this innovation, we have
organized an interview with Dr. Vorp, head of the Vascular
Tissue Vorp Lab here at the University of Pittsburgh. This lab
focuses on vascular bioengineering research projects,
including a current project that focuses exclusively on TEVG
research.
REFERENCES
[1] M. Cleary, E. Geiger, C. Grady, C. Best, Y. Naito, C.
Breuer. (2012). “Vascular tissue engineering: the next
generation”. US National Library of Medicine National
Institutes
of
Health.
(Online
Article).
http://www.ncbi.nlm.nih.gov/pubmed/22695236
[2] X. Wang, P. Lin, Q. Yao, C. Chen. (2007). “Development
of Small-Diameter Vascular Graft”. World Journal of
Surgery.
(Online
Article).
http://www.ncbi.nlm.nih.gov/pubmed/17345123
[3] Shannon L. M. Dahl. (2011). “Readily Available TissueEngineered Vascular Grafts”. Science Translational
Medicine.
(online
article).
http://www.perruchenautomne.eu/biblio/readily%20availabl
e%20tissue%20enineered%20vascular%20graft%20science
%20translationnal%20med%202011.pdf
ANNOTATED BIBLIOGRAPHY
C. Mitcham. (2005). “Bioengineering Ethics”. Encyclopedia
of Science Technology and Ethics. (Encyclopedia).
The Encyclopedia of Science Technology and Ethics
provides an unbiased perspective on the direct laws of ethics
that must be followed when pursuing the field of
bioengineering. As the innovative TEVG deals with stem cell
manipulation of humans, it is evident that some ethical
questions will be raised. This document will allow us to
Snyder
Mattis
clearly and informatively address the ethical concerns
associated with the TEVG.
is uniquely demonstrates implanting a TEVG in a lamb and
an in vivo monitoring system as well. This will be an integral
part of our discussion of current testing and measurement
methods of the TEVG.
H. Kurobe, M. Maxfield, C. Breuer, T. Shinoka. (2012).
“Concise Review: Tissue-Engineered Vascular Grafts for
Cardiac Surgery: Past, Present, and Future.” Stem Cells
Translational
Medicine.
(Online
article).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659720/
This article, from the journal of Stem Cells and
Translational Medicine, specializes in the history as well as
past accomplishments of the TEVG, including the first preclinical tests on different types of animals. This progressed
into the first FDA approved clinical trial for pediatric cases.
This information helps give us a history of the TEVG,
demonstrates how far the TEVG innovation has progressed,
and shows the potential it holds for the future.
S. L. M. Dahl. (2011). “Readily Available Tissue-Engineered
Vascular Grafts”. Science Translational Medicine. (online
article).
http://www.perruchenautomne.eu/biblio/readily%20availabl
e%20tissue%20enineered%20vascular%20graft%20science
%20translationnal%20med%202011.pdf
Published by the American Association for the
Advancement of Science, the Science Translational Medicine
magazine is a research article extensively detailing the
experiments and trials that have already been performed
involving the TEHV. This source’s research information
regarding preclinical testing will be vital for our paper as we
discuss the progress and success the TEHV has had in the
past.
J. Patterson, T. Gilliland, M. Maxfield, S. Church, Y Naito,
T. Shinoka, C. Breuer. (2012). “Tissue-engineered vascular
grafts for use in the treatment of congenital heart disease:
from the bench to the clinic and back again.” US National
Library of Medicine National Institutes of Health. (Online
Article). http://www.ncbi.nlm.nih.gov/pubmed/22594331
Taken from the National Library of Medicine National
Institutes of Health, this academic article describes the
condition known as congenital heart defect (CHD) in
pediatric cases. It is one of the main conditions that the TEVG
will be able to help treat after its development. We intend on
performing a comprehensive analysis of this disease, as well
as on the treatment process for children that have CHD.
T. Shin’oka , G. Matsumura, N. Hibino, Y. Naito, M.
Watanabe, T. Konuma, T. Sakamoto, M. Nagatsu, H.
Kurosawa. (2005). “Midterm clinical result of tissueengineered vascular autografts seeded with autologous bone
marrow cells.” The Journal of Thoracic and Cardiovascular
Surgery.
(Online
Article).
http://www.sciencedirect.com/science/article/pii/S00225223
05001297
Published in the Journal of Thoracic and Cardiovascular
Surgery, this academic research article provides a full account
of clinical midterm results of the TEVG seeded by bone
marrow cells. This specific type of cell is one of the
possibilities that can be seeded onto the TEVG scaffolding.
These halfway results will provide the foundation for our
section that describes the models utilizing mesenchymal bone
marrow cells.
M. Cleary, E. Geiger, C. Grady, C. Best, Y. Naito, C. Breuer.
(2012). “Vascular tissue engineering: the next generation”.
US National Library of Medicine National Institutes of
Health.
(Online
Article).
http://www.ncbi.nlm.nih.gov/pubmed/22695236
This academic article published by the US National
Library of Medicine National Institute of Health. This article
thoroughly describes precisely how the TEVG are made as
well as the different methods and materials that can be used
to create them. This information will be effective as we
describe the primary method of construction, and later as we
specify the different types of biomaterials that are available to
be used.
X. Wang, P. Lin, Q. Yao, C. Chen. (2007). “Development of
Small-Diameter Vascular Graft”. World Journal of Surgery.
(Online
Article).
http://www.ncbi.nlm.nih.gov/pubmed/17345123
The scholarly article on the development of small diameter
vascular grafts was not only printed in the World Journal of
Surgery, but it was also presented at the Molecular Surgeon
Symposium on vascular conditions. The paper not only
describes the TEVG, but also explores other options for
alternatives of vascular grafts. These alternatives will allow
us to illustrate the superiority of the TEHV.
M. T. Koobatian, C. Koenigsknecht, S. Row, S. Andreadis D.
Swartz. Surgical Technique for the Implantation of Tissue
Engineered Vascular Grafts and Subsequent In Vivo
Monitoring. J. Vis. Exp. (98), e52354, doi:10.3791/52354
(video)
http://www.jove.com/video/52354/surgicaltechnique-for-implantation-tissue-engineered-vascular-grafts
(2015).
This video was made by the University of Buffalo’s
School of Medicine. Funded by the National Heart and Lung
Institute, the University directed research for surgical
implantation and in vivo monitoring of the TEVG. This video
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