Session A3
Paper 6017
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.
TISSUE ENGINEERING THE LUNG
Lacey Kostishack, (lmk92@pitt.edu), Mahboobin 10:00, Lindsey Ngau, (len20@pitt.edu), Bursic 2:00
Revised Proposal — Tissue engineering of the lung has
created a novel approach in the treatment of pulmonary
disease and is a viable substitute for lung transplants. This
method consists of two main processes: decellularization and
recellularization. Decellularization uses a combination of
detergents to wash and remove the native cell population from
donated lungs and other mammalian lungs while maintaining
the characteristics and structure of the organ [1]. During
recellularization, the cells are promoted to attach, migrate,
and proliferate to mimic the original lung [2]. The lung
consists of over forty cells types; due to the complexity of the
lung, the recellularization of the scaffold requires precise
cells at various stages of differentiation and at specific
locations for successful tissue regeneration [1]. Cells needed
for recellularization are usually obtained from pluripotent
stem cells. Other sources of these cells include: bone marrow,
stillborn fetal lungs, rats, and the patient [3, 4]. The
advancements being made in lung tissue engineering are the
beginning of the solution to pulmonary diseases.
According to the National Heart, Lung, and Blood
Institute, lung diseases have caused an estimated 235,000
deaths is the U.S. in 2010 [5]. Many of these lung diseases,
such as chronic obstructive pulmonary diseases (COPD),
idiopathic pulmonary fibrosis (IPF), and cystic fibrosis, have
no cure and the susceptibility of lung diseases is expected to
increase greatly by 2020 [1]. For many patients, lung
transplants are the only treatment option; however,
according to the U.S. Department of Health & Human
Services, as of January 1, 2016, there are 1,539 patients on
the organ donor list for a lung transplant [6]. Unfortunately,
the wait for a lung transplant is about four to ten months [7,
3]. By this time, the procedure is no longer as beneficial due
to the deterioration of the patient’s condition and the
increased operational risks [7, 3]. In fact, the five-year
survival rate of the patient after transplant is less than fifty
percent [7, 3]. As such, it is imperative that more research
and energy is spent on tissue engineering the lung so that
patients with lung diseases have a greater chance of survival.
The paper will discuss tissue engineering as a whole,
leading into a more centralized discussion of
decellularization and recellularization. A brief overview will
be given of the pulmonary diseases that require treatment
through lung transplants. After, a portion of the paper will
analyze the contributions tissue engineering will have on
University of Pittsburgh Swanson School of Engineering 1
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treatment options. The paper will also consider the possible
challenges and ethical issues with lung tissue engineering.
Resources that will be used include but are not limited to:
scholarly articles, medical journals, national statistics, and
doctors participating in the regenerative medicine research
at UPMC.
REFERENCES
[1] H. Kubo. (2012). “Tissue Engineering for Pulmonary
Diseases: Insights from the Laboratory.” Respirology.
(Online Article).
http://web.b.ebscohost.com/ehost/pdfviewer/pdfviewer?sid=
b80a579d-521c-4e6e-9650a6d4ec49fbe8%40sessionmgr110&vid=10&hid=106. pp.
445-452
[2] D. E. Wagner, R. W. Bonvillain, T. Jensen, et al. (2013).
“Can stem cells be used to generate new lungs? Ex vivo lung
bioengineering with decellularized whole lung scaffolds.”
Respirology. (Online article). DOI: 10.1111/resp.12102
[3] Y.S. Prakash, D.J. Tschumperlin, K.R. Stenmark. (2015).
“Coming to Terms with Tissue Engineering and Regenerative
Medicine in the Lung.” Perspectives. (Online Article).
http://ajplung.physiology.org/content/309/7/L625.full.pdf+ht
ml? pp. L625-L632
[4] M. E. D. Paepe, S. Chu, N. Heger, et al. (2011).
“Resilience of the human fetal lung following stillbirth:
Potential relevance for pulmonary regenerative medicine.”
Informa
Healthcare.
(Online
article).
DOI:
10.3109/01902148.2011.641139
[5] “Lung Disease Statistics.” National Heart, Lung, and
Blood
Institute.
(2010).
(Online
article).
http://www.nhlbi.nih.gov/about/documents/factbook/2012/c
hapter4
[6] “Organ Procurement and Transplantation Network.” U.S.
Department of Health & Human Services. (2016). (Online
article).
http://optn.transplant.hrsa.gov/converge/latestData/rptData.a
sp
[7] M. Valapour, M. A. Skeans, B. M. Heubner, et al. (2013).
“OPTN/SRTR 2013 Annual Data Report: Lung.” American
Journal
of
Transplantation.
(Online
article).
http://onlinelibrary.wiley.com/doi/10.1111/ajt.13200/epdf
Lacey Kostishack
Lindsey Ngau
ANNOTATED BIBLIOGRAPHY
S.F. Badylak, D. Taylor, K. Uygun. (2011). “Whole-Organ
Tissue Engineering: Decellularization and Recellularization
of Three-Dimensional Matrix Scaffolds.” Annual Reviews.
(Online
Article).
http://www.annualreviews.org/doi/abs/10.1146/annurevbioeng-071910-124743
Published by researchers of the University of Pittsburgh,
this article outlines methods of decellularization and
recellularization for several organs. Although general, the
article details specific processes for decellularizing the
lung. In explaining the recellularization process, cell type
sources are outlined, providing specifics for the lung,
including fetal cells, inducible pluripotent stem cells, and
progenitor cells. This will be useful when discussing the
recellularization process and sources of cell types needed.
J. L. Balestrini, A. L. Gard, A. Liu, et al. (2015). “Production
of decellularized porcine lung scaffolds for use in tissue
engineering.” The Royal Society of Chemistry. (Online
article). DOI: 10.1039/c5ib00063g
This article, submitted by researchers from Department of
Biomedical Engineering and Department of Pathology at Yale
University, presents an improved decellularization protocol
for porcine lungs that effectively removes native cells while
preserving critical ECM components. This entire process can
be performed on adult-sized lungs in approximately 24 hours.
This article will be used to highlight the significant
advancements that have been made on the decellularization
protocol.
R. W. Bonvillain, M. E. Scarritt, N. C. Pashos, et al. (2013).
“Nonhuman
Primate
Lung
Decellularization
and
Recellularization Using a Specialized Large-organ
Bioreactor.” Journal of Visualized Experiments. (Online
article). DOI: 10.3791/50825
This article, submitted by researchers of Tulane University
School of Medicine and Tulane National Primate Center,
outlines
the
preparation,
decellularization,
and
recellularization processes of the lung of a rhesus macaque.
Alternative approaches and results are discussed following
the procedure. To provide further insight, sequenced images
and a video of the experiment are attached. This source will
allow us to describe the engineering process behind
decellularization and recellularization.
J. Lowenthal, J. Sugarman. (2015). “Ethics and Policy Issues
for Stem Cell Research and Pulmonary Medicine.” Chest.
(Online
article).
http://search.ebscohost.com/login.aspx?direct=true&db=aph
&AN=101434099&site=ehostlive. pp. 824-832
This medical article discusses ethics regarding stem cell
research and pulmonary medicine. The article outlines
University of Pittsburgh Swanson School of Engineering 2
2016-01-29
specific stem cells used in regenerative medicine and tissue
engineering and the controversies surrounding each. This
information will be beneficial to our paper as we will discuss
the importance of using stem cells to recellularize a lung
scaffold. Understanding the context of these ethical issues
will help to establish a responsible use of stem cells.
“Lung Disease Statistics.” National Heart, Lung, and Blood
Institute.
(2010).
(Online
article).
http://www.nhlbi.nih.gov/about/documents/factbook/2012/c
hapter4
This article, from the National Heart, Lung, and Blood
Institute, under the U.S. Department of Health & Human
Services, gives detailed statistical analysis of lung diseases in
the U.S. The article examines death rates, prevalence, and
economic costs. This information will be used to illustrate the
trend of the increasing prevalence of lung diseases and the
necessity of creating a viable and renewable source of lungs
to treat patients.
Y.S. Prakash, D.J. Tschumperlin, K.R. Stenmark. (2015).
“Coming to Terms with Tissue Engineering and Regenerative
Medicine in the Lung.” Perspectives. (Online Article).
http://ajplung.physiology.org/content/309/7/L625.full.pdf+ht
ml? pp. L625-L632
This article, specializing in bioengineering the lung,
details challenges in pulmonary tissue engineering. The key
issue is minimizing the probability of organ rejection. To do
this, it is important to focus on the decellularization process,
maintaining the structure and cells needed, and the
recellularization process, utilizing the correct cells for
seeding. This information will be used to propose challenges
still faced, and offer reason to continue research in the field.
M. E. Scarritt, N. C. Pashos, and B. A. Bunnell. (2015). “A
review of cellularization strategies for tissue engineering of
whole organs.” Frontiers in Bioengineering and
Biotechnology.
(Online
article).
DOI:
10.3389/fbioe.2015.00043
This article, submitted by researchers of Tulane University
School of Medicine and reviewed by experts from the
University of Torino, Italy, emphasizes the importance of
preserving the ECM composition and structure while
removing as much cell debris as possible. This information
will be used to describe the architecture and protein
components of the decellularized lung and how combinations
of detergents can be used to preserve and improve the lung
scaffold.
T. Tsuchiya, A. Sivarapatna, K. Rocco, et al. (2014). “Future
prospects for tissue engineered lung transplantation:
Decellularization and recellularization-based whole lung
regeneration.” Organogenesis. (Online article). DOI:
10.4161/org.27846
This article, written and peer-reviewed by researchers
from the Department of Anesthesia and Biomedical
Lacey Kostishack
Lindsey Ngau
Engineering at Yale University and the Nagasaki University
Graduate School of Biomedical Sciences, describes the
different types and combinations of detergents used to
decellularize the lung as well as discuss the different possible
species used in lung tissue engineering. This information will
primarily be used to discuss the different methods of
decellularization.
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