MadSci Network: Immunology

Re: which allograft proteins must be removed in order not to be rejected

Date: Mon Jun 28 12:13:47 2004
Posted By: Michel Ouellet, Projects leader
Area of science: Immunology
ID: 1074115125.Im


As for any allograft, the main cause of the immune reaction of the host 
against the graft and of the graft against the host, is the presence of 
cells expressing major and minor histocompatibility complex molecules.  It 
is thus preferable to remove marrow content from the bones as it contains 
a lot of cells capable of inducing immunity.  Irradiation of the graft is 
an interesting technique being developed as it not only sterilizes it but 
also limits the ability of the graft cells to divide, thus limiting the 
host immune reaction against them.  Once the graft is implanted, it is 
colonized by the host stem cells that ensures growth and regeneration of 
the bone structure. 

Here is an excerpt from the following source:
Arthroscopic allograft surgery of the knee and shoulder: indications, 
techniques, and risks 
Walter R. Shelton M.D.
Arthroscopy: The Journal of Arthroscopic & Related Surgery Volume 19, 
Supplement 1 , December 2003, Pages 67-69 December 2003 Instructional 
Course Lectures Supplement 

" Research is presently ongoing to improve allograft sterility. One is the 
Biocleanse technique[6] (Regeneration Technologies, Gainesville, FL). The 
process uses low temperature chemical sterilization, and more than 300,000 
of the grafts have been implanted with no known infections. The process 
has been validated by the FDA to kill implanted spores and viruses.

Another sterilization technique is the use of high-dose gamma radiation. 
Two to 3 Mrads are routinely used to kill surface bacteria, but this level 
does not kill implanted spores and viruses. Use of high-dose gamma 
radiation exceeding 5 Mrads kills spores and viruses but destabilizes the 
protein of the allograft tissue. Research aimed at stabilizing graft 
proteins while allowing high-dose radiation is ongoing.

A 1985 case from Virginia suggested that freeze drying grafts removed the 
HIV virus. One donor subsequently proven to be HIV positive infected 
multiple recipients. No recipients of a freeze-dried graft converted 
positive to HIV, whereas recipients of fresh and fresh frozen grafts did. 
Recent research has shown that freeze drying removes 99.9% of HIV virus 
but does nothing to remove spores and is only minimally effective in 
eliminating hepatitis C virus. Other infectious agents continue to be a 
concern, especially recent viral illnesses such as West Nile virus and 
SARS. The job of allograft sterilization only promises to become more 

The most common way that tissue banks process allografts is sterile 
harvest and procurement. Grafts may be stored in 4 different methods. The 
first is a fresh allograft. The allograft must be implanted within 24 to 
48 hours after harvest. Cooling the allograft to 4C can slightly extend 
this period. The second is fresh freezing to −80C to −196C. The grafts 
can be stored for 3 to 5 years. The donor cells in the allograft are 
killed by fresh freezing. The third method is cryopreservation, a process 
of controlled rate freezing to −196C, while cellular water is extracted 
by dimethylsulfoxide and glycerol. Up to 80% of donor cells can survive, 
and the graft has a 10-year shelf life. Freeze drying is the fourth method 
and uses freezing and lypophilization to a residual moisture of less than 
5%. The graft can then be stored from 3 to 5 years at room temperature.

Allografts undergo 4 stages during healing. The first stage is cellular 
death within the graft, occurring during procurement or shortly after 
implantation. The second is revascularization of the graft with new host 
blood vessels. Third is cellular repopulation of the graft by the host, 
which occurs rapidly and can be complete as early as 6 weeks post 
implantation. The fourth is remodeling of the allograft, requiring as long 
as 18 months for completion.

Donor cellular elements on allograft bone, cartilage, and tendons do 
produce a classic, but clinically limited immune response. This reaction 
can be minimized by removing marrow elements during processing. The cells 
in cartilage and menisci are deeply imbedded in an avascular matrix, and 
this insulation from the host immune system may also help to explain the 
limited antigenic response seen with allografts. Despite this subclinical 
response, immune markers can be recovered from joint fluid after an 
allograft has been implanted.

The use of an allograft can produce a significant and dramatic improvement 
in a recipient when used in the appropriate manner. Implanting surgeons 
should be aware of the benefits of allografts, but they should also be 
very aware of the potential hazards including viral and sporeform 
infections. One should be completely familiar and comfortable with the 
tissue bank that processes your allograft, thereby insuring the patient is 
receiving the highest quality possible."

I hope this answered your question.

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