Running head: RESEARCH ON EXTRACELLULAR MATRIX
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Further Research on Extracellular Matrix’s Side Effects and Solutions by Literature Review
Junchen Liu
ENGL 106i
Kyongson Park
March 27th, 2015
Purdue University
Author Note
Junchen Liu, Department of Engineering, Purdue University.
Junchen Liu is now at Department of Engineering, Purdue University.
Correspondence concerning this article should be addressed to Junchen Liu,
Department of Engineering, Purdue University, West Lafayette, IN, 47906.
Contact:liu1320@purdue.edu
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Abstract
This thesis is a synthesis paper targeting at the transplantation rejection caused by the
extracellular matrix and the possible treatment for the rejection. Coito and Kupiec-Weglinski
(2000)found out the relationship between the extracellular matrix and the transplantation
rejection while Kirk and his teammates (1999) found out an effective suppressor for the acute
transplantation rejection and the Dr. Libby and Pober stated that the chronicle transplantation
rejection, which is transformed from the acute transplantation rejection, has no antidote. This
paper shows to what extent the side effect of the extracellular matrix, the transplantation
rejection can be cured. In all, the in the acute rejection phase, the symptom is still curable, but
once the acute rejection transformed to the chronicle rejection phase, the side effect can’t be
cured.
Keyword: Extracellular matrix, the acute transplantation rejection, the chronicle
transplantation rejection
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Further Research on Extracellular Matrix’s Side Effects and Solutions
My research focus is on the side effect of the extracellular matrix. Now I am currently
researching the most significant side effect – the transplantation rejection. Now, I am research
through two research questions:” To what extent will the extracellular matrix be related to the
transplantation rejection?” and “What is the available most effective suppressor of the
transplantation rejection?”
Coito and Kupiec-Weglinski (2000) from Harvard University studied the components of
extracellular matrix by using different combination of the components and implemented them
on rats with the transplanted organs. They added the fibronectin and the laminin, both of them
are one of the components is extracellular matrix. They observe the acute rejection, which is
the rejection that will be developed as early as one week after the transplantation. They also
found out the newly synthesized fibronectin, but not the laminin, from the transplantation will
increase the likelihood of the acute and late rejection. Coito (2000) finally concluded that the
fibronectin, a protein in the extracellular matrix “are active participants in the immune
cascade leading to graft rejection.” (p.2467), which means it may lead to the rejection of the
transplantation.
What Coito and Kupiec-Weglinski (2000) stated is evident, and the experiment in the
thesis shows me the reason and the correlation between transplantation rejection and the
extracellular matrix. I figured one thing that is very interesting is that what they stated in their
paper is only about the organ transplantation rejection, so I think that the muscle have no
rejection reaction. I would concluded from this thesis that extracellular matrix did cause the
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rejection to some extent. From now on, I will focus on solution for two steps, each for a type
of rejection of the transplantation of the organs, but not the muscles.
Kirk and his teammates (1999) experimented with CD154 (C1), a specific protein that
will activate the immune system and claimed that the C1 is “a promising agent for clinical
use in human allotransplantation” (p.686), a transplantation from the same species. Firstly
they deducted that the CD40 (C2) is an essential component in our body to mediate the
immune and inflammatory system, and C1, the suggested antidote, works as a pair to
suppress the C2 to activate unnecessary immune reaction. When there are significant amount
of the foreign matter attack the body, C2 will be concentrated and overwhelm the effect of C1,
which will cause the immune system to reject the foreign matters, so the researchers will
inject C1 to suppress the excessive amount of the C2 to soothe the rejection system. They
used monkey to do the renal (kidney) transplantation and inject with C1D154. The acute
rejection was suppressed after the injection. They then observed the monkey and concluded
that the C1 can suppress the acute rejection for a time as long as 10 months. And more
surprisingly, they found out that there is no additional need to do more treatment to prevent
the graft loss, as known as the transplanted organ lost. Also, research has found out that the
existence of C1 after the treatment is not required by using antibody to eliminate the C1. The
advantages of this treatment is that it doesn’t need to suppress the immune system all around
the body. So this is an effective antidote to confront the acute rejection.
Even though Kirk and his teammates (1999) claimed that the CD154 was very useful,
from what I think it was still not a success because it still can’t change the fact that the acute
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rejection will become chronicle rejection if not controlled (Libby & Pober, 2001). It is
probably the most effective suppressor now. Hence, it would be a very useful reference for
developing the suppressor. After knowing this, I would examine the only kind of rejection left,
chronicle rejection.
Libby and Pober (2001) stated that the chronicle rejection will result in the loss of the
transplanted organs, so that eventually the patients will lose the organs which are consumed
by the immune system. The cause of the chronicle rejection can be resulted from the failure to
suppress the acute rejection. The researchers stated that the 5% of the acute rejection will fail
and develop into chronicle rejection. They suggested that the patient take the therapy for the
acute rejection continuously even though the affect would be petite. They also pointed out
that the suppressor of the acute rejection may be the cause of the chronicle rejection because
it may target at wrong mechanism. Till now, there is no possible antidote to defeat the
chronicle rejection.
I feel really unsatisfied by this result, but I guess I have to accept it. I speculated that the
chronicle rejection is what left after the unsuccessful treatment for the acute rejection. The
only way to lower the possibilities to get the chronicle rejection is to use a better version of
the suppressor for the acute rejection in an appropriate time.
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Conclusion
From this paper, the fact that extracellular matrix can induce the organ transplantation,
which is a hindrance for organ regrowth because this technology uses the extracellular matrix
for other sources is evident. This paper also talks about how the CD154, a suppressor for
acute rejection. This suppressor is a very potential one to cease the acute rejection but not
effective to help prevent the acute rejection converting into chronicle rejection. Lastly, the
most deadly kind of rejection, chronicle rejection has sadly no effective cure. The only
method I suggest is to treat the acute rejection at a precise time with a precise amount to
prevent it changing into chronicle rejection.
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References
Andrews, W. (2008, February 7). A "Holy Grail" Of Healing. Retrieved March 27, 2015,
from http://www.cbsnews.com/news/a-holy-grail-of-healing/
Coito, A. J., & Kupiec-Weglinski, J. W. (2000). EXTRACELLULAR MATRIX PROTEINS
IN ORGAN TRANSPLANTATION1. Transplantation, 69(12), 2465-2473.
Kirk, A. D., Burkly, L. C., Batty, D. S., Baumgartner, R. E., Berning, J. D., Buchanan, K., ... &
Harlan, D. M. (1999). Treatment with humanized monoclonal antibody against CD154
prevents acute renal allograft rejection in nonhuman primates. Nature medicine, 5(6),
686-693.
Libby, P., & Pober, J. S. (2001). Chronic rejection. Immunity, 14(4), 387-397.