Progress in Xenotransplantation

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Progress in Xenotransplantation

Introduction

In the last few years, progress has been made toward successfully using animal organs in humans who need transplants, an operation called xenotransplantation. The biggest obstacle has been preventing the body from destroying the transplant as a foreign body. The speed of rejection depends on the species and tissue involved. In transplants between discordant species, such as pig to human, the recipient has natural antibodies against the donor organ. In untreated discordant vascularized xenografts, hyperacute rejection (HAR) occurs within minutes or hours after transplantation.

Recently, HAR has been successfully inhibited, and a second stage of rejection, termed delayed xenograft rejection (DXR), has surfaced. DXR takes place three to four days after transplantation and results from a cell-mediated response. Such a response involves a massive invasion of macrophages, which engulf the xenograft cells. Successful suppression of DXR is currently the most researched area of xenotransplantation because this stage of rejection must be inhibited before even later types can be researched.

Hyperacute Rejection (HAR)

The Immune Response that Causes HAR

Several researchers have evaluated the specific antibody response that is responsible for HAR. An in vitro kinetic experiment combined rat endothelial cells with primate serum and then measured bound human and monkey antibodies, number of lysed cells, and C complement activity (Azimzadeh et al., 1996). The results showed that IgM antibodies were produced rapidly in the earliest stage, after which a large number of IgG antibodies were produced. Components of the C cascade were present on the endothelial cells. Th...

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....G White. 1995. Endothelial Expression of Human Decay Accelerating Factor in Transgenic Pig Tissue: A Potential Approach for Human Complement Inactivation in Discordant Xenografts. Transplantation Proceedings27: 326–327.

Schmoeckel M., G. Nollert, M. Shahmohammadi, V.K. Young, G. Chavez, W. Ksper-Konig, D.J.G. White, J. Muller-Hocker, R.M. Arendt, U. Wilbert-Lampen, C. Hammer, and B. Reichart. 1996. Prevention of Hyperacute Rejection by Human Decay Accelerating Factor in Xenogeneic Perfused Working Hearts. Transplantation62: 729–734.

Wennberg, L., C.G. Groth, A. Tibell, S. Zhu, J. Liu, E. Rafael, J. Soderlund, P. Biberfeld, R.E. Morris, A. Karlsson-Parra, and O. Korsgren. 1997. Triple Drug Treatment with Cyclosporine, Leflunomide and Mycophenolate Mofetil Prevents Rejection of Pig Islets Transplanted into Rats and Primates. Transplantation Proceedings29: 2498.

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