Donor Pig Breeding

China has abundant pig resources, our previous work is mainly to pig breed for islet xenotransplantation, through the early 5 years of screening, we found that in the closed area of our country some special landform and special climate, have some kind of special pig, the pig is very good for xenotransplantation the donor potential, there is no other mainstream countries present the advantages of xenotransplantation. After that, we again after 7 years of efforts, we have established a suitable donor pig islet xenograft and conforming to the international standard of inbred lines, with full independent intellectual property rights, at the same time, we established the first Asia Pacific region with WHO and standard with independent intellectual property rights of medical grade donor pig production base.

The most important is the team of Professor Wang Wei after more than 10 years of efforts, through careful cultivation for islet xenograft donor pig inbred pig breeds (species number one) has ruled out between pig and human all cross species infection pathogens (including retroviral PERV and WHO, the International Xenotransplantation Association designated at the same time, microorganisms) also excluded PERV self replication and gene recombination and related viruses may solve a major doubts there may be security risks of xenotransplantation, this is an important breakthrough in swine Xenotransplantation on biosafety.

With the Sino biological cultivation of donor pig inbred pig breeds (species number one) isolated islet cells with high activity, the cell efficiency, high extraction efficiency and separation after transplantation of high security four advantages, this is the first developed in China, with excellent islet xenotransplantation independent intellectual property rights of donor pigs.



Xenotransplantation and donor pigs


With the progress and development of regenerative medicine, organ transplantation has become the first choice of treatment for many end-stage diseases. There are hundreds of thousands of transplant recipients of heart, liver and kidney all over the world. With the success of surgery and the continuous development of immunosuppressive agents, the success rate of transplantation is becoming higher and higher. At present, the main source of organ transplantation is brain death, and the shortage of donor organ is seriously perplexing the promotion and application of organ transplantation. Therefore, in the situation where donor organs are in short supply, scientists have focused their eyes on xenotransplantation of animal sources. The first element of xenotransplantation is the demand for donor animals, and the most critical is the biological safety of animals and the effectiveness of the transplanted animals.


I. Biological safety of xenotransplantation donor
The WHO has specific requirements for the biosafety of xenotransplantation.
1. The "Changsha declaration" of the United Nations WHO (WHO)
In November 2008 the UN China WHO, the Ministry of health and the Central South University jointly sponsored the "global xenotransplantation standard clinical research international symposium held in Changsha, meeting established global guidance xenotransplantation research and development of a programmatic document ---" Changsha declaration". In the "Changsha declaration" on biological safety, WHO believes that:
A. The clinical application of xenotransplantation needs to be effectively supervised. Every member country should formulate relevant laws and regulations to ensure that there are enough regulations and regulations in the country to regulate and prohibit illegal or standard xenotransplantation.
B. xenotransplantation cells, tissue and organ donors must be produced under strict quality standards to ensure their quality and biological safety.
C. according to WHO‘s regulation, at present, only Designated Pathogen Free Pig, which is in line with the standard, can be used as a donor source for clinical research of xenotransplantation. The specified pathogen is referred to as xenotransplantation donor pigs could not be detected WHO specified by the hundreds of species of bacteria, fungi, parasites and viruses, namely SPF pig (from birth to Yu Chengdu specific pathogen free microbial diseases and parasitic diseases of pigs) by caesarean section (uterine incision delivery) in newborn piglets obtained, feeding in gnotobiotic animal isolator conditions, under the condition of GMP for cultivation of adult pigs after the formation of the second generation, the detection of non specified pathogens, namely no specified pathogen of swine (DPF pigs), also known as medical grade donor pigs.
2. Avoid potential endanger of endogenous retrovirus
In 2000, studies on porcine xenotransplantation suggest that the porcine endogenous retrovirus (PERV) has a potential risk of cross strain infection. PERV exists in the genome of most mammals, including pigs. Under normal conditions, the virus neither replicates nor expresses in the host cell, or is very inefficient in expression, and rarely causes damage to the cells. However, once they cross the interspecific barrier, they are likely to proliferate in the body of the Shinjuku. The results of recent studies show that the potential risk is very small. This danger has been eliminated by Professor Wang Wei and foreign scientists, in particular, to cultivate the missing donor pigs of the PERV-C subtype.
In the end, the current clinical application of xenotransplantation in disorder in immune xenogeneic rejection, biological safety is one of the most concern, with the biological safety standard should be excluded from the porcine endogenous retrovirus medical grade donor pigs (DPF pigs).

II. The requirements of xenotransplantation effectiveness to donor pigs

The current research shows that the key to the effectiveness of xenotransplantation is how to eliminate immune rejection in xenotransplantation. Xenotransplantation and xenotransplantation have a large difference in the mechanism and treatment of immune rejection.
1. The requirement of xenotransplantation for donor pigs
At present, the research on xenotransplantation porcine islet cells and nerve cells mainly concentrated in pigs, because these two kinds of cells lacking other cells in pig alpha -1, 3 Gal antigen, so transplantation into the human body immune rejection is weak, no other tissue and organ xenotransplantation of hyperacute rejection and this greatly increased the success rate of xenotransplantation. According to a large number of research results at home and abroad, the first possibility to enter clinical trials and have significant social significance and economic value is islet cell transplantation for diabetes mellitus and neural cell transplantation for the treatment of Parkinson‘s disease. As long as the biosafety problem is solved, the immunological rejection of porcine islets and porcine nerve cells can be controlled by the current clinically available scheme. There is no need for the donor pigs.
2. The requirements of xenotransplantation for donor pigs
Pig organs are similar to human organs in structure, size and physiological function, and have been the main research object of xenotransplantation. The biggest problem with pig organs as organ donors in xenotransplantation is hyperacute rejection, because of the existence of a non primate animal alpha -1, 3 Gal antigen, when the transplantation of pig organs into humans, cells of the alpha -1 galactose 3, will be the immune system to identify, to a few minutes a few hours that lead to the decline of organ transplantation. Now this problem has been solved by scientists. After knocking out the alpha -1, 3, galactotransferase gene of 3, galactose from pig somatic cells, the clone pig produced by nuclear transfer technology will no longer produce alpha -1, 3, galactose antigen. Transplantation of this pig‘s heart to a baboon can survive for 4 months.
After overcoming the hyperacute rejection, it is necessary to solve the delayed rejection and T cell mediated long term immune rejection within a few days of xenotransplantation. Through genetic modification and cloning technology further, and will delay the rejection immune response and T cell mediated rejection related gene knockout or transferred to alpha -1, 3 - galactosyltransferase knockout pigs, will be able to get used to the human organ transplant without causing immune rejection of organ donors. So, with a series of genetic modification, the pigs will cause rejection of the key gene knock down, then add some genes after such "genetically modified" pigs will become a suitable for human, no immunologic rejection of the donor, this is called "pig transgenic pigs". The organ donor, which can be used for human organ transplantation without immune rejection, is the advantage of transgenic pigs.
However, the transformation of transgenic pigs also brings some questions and needs further study. For example: 1) the problem of aging organ, the modified organ is a good life; 2) most of the transformation of the gene belongs to immune defense genes, gene transformation is bound to change the environment stable ability of organ transplantation and local immune surveillance, will increase the incidence of tumor; 3) some transgenic pig tissue and cell secretion of normal human body does not exist the antibody, enters the human body after transplantation will also change the immune environment, whether it will increase the risk of pathogen infection or cause human autoimmune diseases; 4) in addition to consider whether it will cause due to multiple gene transformation of transgenic porcine reproductive and fertility decline or lead to congenital development bad, affect the industrial development in the future. These are all questions that must be answered before the clinical application of transgenic pigs.
Three, high efficiency and high safety "heterologous number one" donor pig
Central South University and Hunan sainuo Biological Technology Co. Ltd, after years of efforts, has been established for porcine islet xenograft and conforming to the international standard of inbred, and was named as the "heterogeneous one"; at the same time the establishment of the Asia Pacific region only a WHO meets the standard and with independent intellectual property rights of medical grade donor pigs (DPF pigs) production base. The "heterologous number one" pig has ruled out the possibility of all the pathogens (including endogenous retrovirus PERV) of all cross species infection in human pigs. "The separation of xenogeneic islet cells, pigs with high activity, the cell efficiency, high extraction efficiency and separation after transplantation of high security four advantages, this is the first independent medical development in China, with independent intellectual property rights of the donor pig species.