|MadSci Network: Immunology|
Hi, 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 (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 difficult. 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 4°C can slightly extend this period. The second is fresh freezing to −80°C to −196°C. 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 −196°C, 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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