As the author of this question, I believe that it is possible that in the future to life, xeno-transplantation, because the currently  sources of organs is very limited!

It is assumed that 25-30 percent of  patients die waiting on waiting lists because they can not get the body!

Of course before that need more work to improve-the discovery of new immunosuppressant, to enhance the possibility to overcome the immuno-biological barriers, improve clinical immunological laboratory tests for the purposes of xeno transplantation, microbiological to lie because most of these animals is infected, probably the new anti infective drugs, etc ..... etc!

I am not optimistic for a success of xeno grafts in the near future. Maybe if new immunomodulators (not yet known) would be tested and applied with positive results, we could expect good issues, but currently not!

Near future it might not be the solution but Xenotransplantation can be bridge until organs available....I think we should work on this hoping some day we will achieve what be hope.

Dear dr.Metodiev, I agree with you currently or in the future we hope to find a better and stronger immunospresiv, which if overcome immune barriers of different species-and allows start successful xeno-transplant!

Dear dr.Vimukthi Pathiraja, I agree with you currently or in the future that we will later study and the findings of new immunosuppressive and improvements and other things such as immunological laboratory diagnostics,microbiology,   infectious diseases (because most of these animals is infected) etc. successful start xeno-transplant!

I forgot to tell you one good example from the history of transplantation, the discovery of a single drug immunosspresiv Cyclosporin, eighties made a revolution in transplantation! Before it was also this discipline quite backwater!

I hope the same scenario, and now when it comes to start xeno-transplantation!

Frankly I am surprised that industry has been so slow at creating a mechanical heart and possibly a lung or a kidney.. This would avoid all the problems with the immune system.

Dear dr.Alen,

I fully agree with you when it comes to making mechanical organs, if it is successfully avoid the immune system and all biological barriers which he represents as big problems for the initiation of such a complex process as xenotransplantation!

Dear dr.Alen,

I forgot to say that I am still optimistic that in the future will still become a reality one day xeno-transplantation! The most we hope gives more Seen scenario with the discovery of Cyclosporine, eighties of the last century, which has launched a brand transplantation  organs, which is before his discoveries was to a great stagnation! and now hope that we will reach a new "Cyclosporin" that if you might allow to start working and xenotransplantation!

Happy Easter to all my friends and all members RG around the world!

My opinion is that they must seek and explore alternative sources of organs such as the xeno-transplantation, because the existing is not enough because the higher number of claimants organs from a donor! A large number of patients die on waiting lists, because they can not get the organ they say around 20-25%!

Dear friends, Happy Easter! With all my best wishes!

Please, feel free to join us, 11-14 May 2017, in the Congress Center of Hotel Admiral, Resort Golden Sands, near Varna. The 27-th Annual Assembly of IMAB is open for all colleagues: www.imab-bg.org

See you soon in Varna!

Thank you very much congratulations for Easter!

Thank you very much for inviting me to Congress, I am very grateful!

When I see their obligations, in this period, very soon I will be in touch!

Regards from Sarajevo

Jasenko

I opened a symposium program and saw many interesting things from medicine and a good magazine that gives this company! Varna, I never said in her that it is a beautiful Center-dirt on the Black Sea coast!

If I have time and obligation I will be happy to be part of this symposium in Bulgaria!

Thanks for your information!

Xenotransplantation

Jasenko Karamehić, 

INTRODUCTION

Xenotransplantation is the transplantation of living cells, tissues or organs, from one species to another. Such cells, tissues or organs are called xenografts or xenoternal embryos. Humane xenotransplantation offers potential treatment for the terminal stage of organ failure, which today represents a major global problem. The dimensions of this problem as well as the advances in immunotherapy triggered a great interest in the potential use of animals instead of humans as organ donors. Researchers in this field focused their efforts on suppressing the immune barrier that prevents long-term survival of the xenograft. Xenotransplantation is also linked to many medical, legal and ethical issues. The use of xenotransplantation for clinical purposes would imply a multidisciplinary approach to provide a more complete response to various questions related to the use of xenografts for human purposes. In this regard, safety, ethics and regulatory aspects of xenotransplantation are now working to achieve the best conditions in which the ratio Between risk and benefit was as favorable as possible.

DEFINITION

Xenotransplantation implies any procedure involving transplantation, inplantation, infusion into a human recipient of either living cells or from inhuman animal sources, whether human body fluids, cells, tissues, organs that have exacerbated contravention of living inhuman cells to the tissues or organs.

 (USA Food and Drug Administration / FDA, 1999; FDA, 2001) This is a reference to here the reference number

Xenotransplantation products must be alive. For example, human skin cells that grow outside the body, on the base of inhumane cells, and are used to reconstruct skin in humans, can also be considered a xenotransplantation product. This category of procedure is included in the definition of xenotransplant because, Scientists consider potentially transmitting infection with such procedures to have similarities with the transmission of infection in the transplantation of living animal cells, tissues or rabbits to a human donor.

CURRENT STATUS AND GUIDELINES IN CANCER SUPPLY

It is known that xenotransolants and xenotransplantation products are under regulatory authority of the FDA, the FDA has formulated the BRAMAC / Biological Response Modifiers Advisory Commitite as a current mechanism for open discussion on scientific, medical, ethical and social health issues related to xenotransplantation.

The FDA has developed a xenotransplantable action plan to create one approach to xenotransplantation regulation. This assumption implies regulating issues of public health and safety when it comes to xenotransplantation. In addition, this approach gives guidance to sponsors and researchers on the safety of clinical research and monitoring.

Occasionally, the FDA issues brochures that help researchers and sponsors

 Interested in Xenotransplantation Research. These documents contain guidelines on the safety of xenotransplantation products and the course of clinical research, with particular reference to animal feed procurement and screening qualification recommendations, animal product testing as well as post-transplant monitoring and survival of animal transplant recipients. The FDA notifies and invites the public to comment and discussion on these documents, also organize mitigating and workgroups focused on xenon transplantation issues. Such gatherings help to exchange information and involve the public in xenon transplantation issues.

FUTURE OF CANCER SUPPLY

It might be unusual for a manual that considers practical issues related to the practice of medical disciplines of transplantation and immunology should take into account such a hypothetical topic such as xenotransplantation. In all likelihood, the lack of human organ donors is such a serious problem that interest in xenotransplantation has significantly increased. With the advancement in developing methods that focus on processes:

1.) "Exercise" of human antibodies and on

2.) 2. Inhibition of the complement system, the problem of hyperacid rejection does not seem to be an insurmountable obstacle.

Rather, it could be said that acute vascular rejection, the cause of which is currently unclear, may now appear to be the main humoral barrier of xenotransplantation. If acute vascular rejection can be prevented by approaches that are useful in treating hyperacid rejection, then clinical xenotransplantation may become possible. If there was an accumulation, which would provide resistance to acute vascular rejection, then clinical transplantation could be further developed.

In the future, clinical xenotransplantation can achieve the desired goal of achieving prolonged graft survival, also using lessons from allotransplantation.

REFERENCES

1. Hickman R, Saunders SJ, Goodwin N, Terblance J. Perfusion of the isolated pig liver with human blood. J Surg Res, 1971; 11: 519-527.

2. Cooley DA, Gallman GL, Bloodwell RD, Nora JJ, Leachman RD, Human heart transplantation: experience with 12 cases. Am J Cardiol, 1968; 22: 804-810.

3. Abouna GM, Serrou B, Boehmig HG, Amemiya H, Martineau G. Long-term hepatic support by intermittent multi-species liver perfusions. Lancet, 1970; 2: 391-396.

4. Nalesnik MA, Fung JJ, Strazl TE, Demetris AJ. Pathology studies in two baboon to human liver xenograft cases. Transplant. Proc, 1994; (In press).

5. Auchincloss H Jr. Xenogeneic transplantation. Transplantation, 1988; 46: 1-20.

6. Reemtsma K. Xenotransplantation: a personal history. In: Xenograft 25, Hardy MA, (ed.) New York: Elsevier Science Publishers, 1989; 7-16.

7. Collins BH, Chari RS, Magee JC, Harland RC, Lindman BJ, Logan JS, et al. The immunopathology of porcine livers perfused with the blood of humans with fulminant hepatic failure. Transplantation, 1994; 58: 1162-1171.

8. Welsh KI, Taube DH, Thick M, Palmer A, Stevens N, Binns RM. Human antibodies to pig determinants and their association with hyperacute rejection of xenografts. In: Xenotransplantation. The transplantation of organs and tissues between species, Cooper DKC, Kemp E, Reemtsma K, White DJG, (eds.). New York: Springer-Verlag, 1991; 501-510.

9. Czaplicki J, Blonska B, Relgia Z. The lack of hyperglycogenic xenogeneic heart transplant rejection in a human. J Heart Lung Transplant, 1992; 11: 393-398.

10. Jooste SV, Clovin RB, Winn HJ. The vascular bed as the primary target in the destruction of skin by antiserum. J Exp Med, 1981; 154: 1332-1341.

11. Starzl TE, Fung J, Tzakis A, et al. Baboon-to-human liver transplantation. Lancet. Jan 9 1993; 341 (8837): 65-71.

12. Rood PP, Cooper DK. Islet xenotransplantation: Are we really ready for clinical trials? Am J Transplant. Jun 2006; 6 (6): 1269-74.

13. Chatterjee DS. A controlled comparative study of the use of porcine xenograft in the treatment of partial skin thickness loss in an occupational health center. Curr Med Res Opin. 1978; 5 (9): 726-33.

14. Fink JS, Schumache

CLINICAL EXPERIENCE IN CANCER SUPPLY

Founders of organ transplants are considered Alexis Carell and Charles Guthrie. The development of vascular anastomosis in the early 1900s allowed investigators to develop organ transplantation techniques. Carell and Gutrie, performed replanting of the leg at the dog, and developed a known patch of graft technique to expand narrowed blood vessels. They also worked on heteroropic experimental transplantation. It is important to emphasize that the initial xeno and allotransplant functions only in a short period of time. In these pioneering beginnings, the most common causes of rejection were related to technical problems or substantial incompatibility. In view of this, the application of vascular anastomosis to organ replacement had to wait for the development of effective immunosuppressive therapy that occurred at least 50 years later.

When immunosuppressive agents became available in the early 1960s, human organs were still seldom available, leading the researcher to re-turn to the possibilities of xenotransplantation. In the early 60's, the Reemsthemian scientist succeeded in transplanting a 12-kid kidney series from a monkey chimpanzee to human recipients. The clinical development of these transplants was characterized by episodes of reduced renal function, which is analogous to acute cellular rejection. The transplant was associated with infection with 2 recipients and acute cell refs in 6 recipients. Some of the transplants functioned for months, most of which lasted 9 months. During this period, knowledge of transplantation immunology and immunosuppressive therapy was minimal. Using modern immune-suppressive therapies and antibiotics, these transplants could enjoy a long period of survival.

CLINICAL EXPERIENCE IN CANCER SUPPLY

In the near past, baboon monkeys were transplanted to 2 human subjects with failure, that is by refusing them. Although liver donates from the baboon monkey finally died, it seemed that transplanted organs showed histological signs of rejection.

While the above results may be considered promising, there are serious limitations in the use of non-human mammals of the highest order as organ donors, even if ethical problems can be solved. Many top-level moms are too small, and large moms have not enough to meet the current need for the necessary organs. An important detail for xenotransplantation was observed in the 1990s when a pork retrovirus was detected. The problem associated with the risk of transmitting infection among species has resulted in many clinical studies in the field of xenotransplantation.

 The current technology that could allow genetic engineering of certain animal species can not be applied to humans, and finally, even if the appropriate techniques were developed and solved social issues, the long period between the birth and maturity of the mammal of the highest order reject scientists from this approach.

Bearing in mind the urgent need for organ donors and the problems associated with the use of non-human mammals of the highest order, many researchers focus on strategies that will overcome large immune hurdles when using the highest order mammalian as the organ donor. The animal that proved to be the most suitable for the purpose described above is the pig. Pigs have the appropriate size, and as far as they are known, they are physiologically compatible with humans. Pigs themselves possess relatively few types of microbiological agents that could be transmitted to humans. It is equally important to emphasize that pigs are bred in comparable comparable breeding periods. Finally, we have the technology available to genetically manipulate these animals, allowing us to make appropriate animal-donors be "planned" as providers with the greatest chance of successful transplanting to humans.

Unfortunately, science is faced with huge immune obstacles in transplanting animal organs to humans. Kidneys and heart transplants with non-high-risk mammals on genetically unmanaged people only functioned for a short period of time, if they were functioning at all, and transplant loss was probably caused by hyperacid refusal. Animal livers connected ex vivo to the circulation of patients with liver failure have managed to sustain the lives of several people. The "wear" of anti-contraceptive antibodies prevented hyperacid rejection of xenotransplantation in several reported cases.

Is xenotransplantation real future of organ transplants?. Available from: https://www.researchgate.net/post/Is_xenotransplantation_real_future_of_organ_transplants2 [accessed Apr 22, 2017].

What could be opportunities with xenotransplantation concerning hyperacute organ rejection?

Yes it is a big problem because the immune biological barriers and differences in the HLA complex human species and potential donors from various of species (pig, monkey, etc.) that are large and will create a big problem in all kinds of rejection.

I think that is still a lot has to do in choosing a selection from the pre tipizacion stage and the discovery of stronger and more efficient imunospresiva with fewer unintended consequences!

Very good question and thank you for the good cooperation dr.Delić!

There is another problem that needs to think and who can do tomorrow if we do work, hypothetically ksenotranspntaciju namely:

that many animals are infected and, when we start with immunosuppression, the situation may get worse! I think on this issue should be much, much work!

From your experience, which is the best immunosupresive drug in liver transplant?

Could you please share from your experience which of the following immunosupresive drugs is better: Cyclosporine of tacrolimus in liver transplantation?

Tacrolimus is used in transplantation of liver!

Both make basic immunossuppresion in organ transplant!

Tacrolimus is somewhat pharmacologically  is more  potent  than Cyclosporine but also give something more adwerse reaction!

Thank you for your answer Professor, could you answer me what is your experience with organ rejection after use of these two immunosupresive drugs?

Thanks for interesting question dr.Marina-Delic -Sarac , I will try answer from my experience!

TYPES OF OPENING TYPES

  TYPES OF REJECTION

Jasenko Karamehic, Marc Lorber

Content

1. Types of organ rejection 156

1.1 Introduction 156

2. Activation of the immune system 158

3. Activation of T cells. 158

3.1. Antigen presentation 158

3.2. Other conditions for the activation of T cells 160

4. Activation of B cells 162

5. Hyperacute rejection of graft 163

6. Acute rejection of graft 164

7. Initiation (onset) of acute rejection of graft 164

8. Mechanism of tissue damage 165

8.1. Antibody 165

8.2. Natural killer cells-nk 166

8.3. Specific cytotoxic T cells 166

8.4. Deferred type of hypersensitivity reaction 168

9. Chronic rejection 169

10. Immune system and chronic rejection 172

11. Response to the injury hypothesis 173

12. Conclusion ... .............................................. .................................... 173

13. Literature 174

1. TYPES OF OPENING OF THE AUTHORITY

INTRODUCTION

Transplantation Immunology refers to a large number of events that occur after allograft or xenograft is removed from the donor and transplanted into the recipient. There is damage to tissue both graft and tissue at the site of transplantation. The inflammatory reaction is immediately reported, and an immune response is initiated.

Transplants can be performed in a wide variety of genetic inequalities, from non-mismatch (auto / isograft) levels to the level of marked mismatch (allo / xenograft). Clinically, with the exception of transplants between monozygotic twins, the donor organ and recipient will inevitably be distinguished in one or more genetic loci, some of which may be recognized as foreign.

Locuses of Class I and Class II, a large complex of histocompatibility of MHC, due to their large polymorphism in turn, create the biggest problem in this area. Although differences in the smallest locuses may also produce an immune response, which is partly a problem in bone marrow transplantation.

Autograft: Transplantation of a person's tissue from one place to another.

Isograft / Synergistic or Isogenic Graft: Transplantation of tissues between genetically identical individuals, e.g. cadaveric transplantation between monozygotic twins.

Alograft / Alogeni graft: Transplantation between genetically different members of the same species, e.g. cadaveric transplantation between unrelated individuals.

Xenograft: Transplants between members of different species, e.g. from a monkey to a man.

Recipes that have previously been sensitized to donor graft antigens show hyperacute transplant rejection due to the presence of antibodies formed in the circulation. The cross-examination test, routinely performed before clinical transplantation, detects such antibodies.

In case the test is positive, transplantation is not performed. Despite the use of potent immunosuppressive drugs such as Cyclosporin and FK506, many patients have been diagnosed with an acute clinical rejection episode in a short period after transplantation.

These episodes are usually reversible, which is supported by increased doses of conventional drugs or the addition of antibody therapy, but will inevitably cause a certain level of graft damage. This damage can contribute to long-term degeneration or chronic rejection of graft. Accordingly, it is clear that all rejection types are associated with an immune response to donor antigens.

2. ACTIVATION OF THE IMMUNE SYSTEM

Invasion of the body by any foreign material leads to a series of events that result in its expulsion. Generally, these events include non-specific inflammatory and antigen-specific immune responses. Both responses were widely conducted with leukocytes from the bone marrow.

A specific immune response was mediated by T cells originating from thymus and antibody producing B cells. T lymphocytes are the leading in the immune response, once activated by antigen, induces differentiation and activation of many other cells. The immune response is supported by many cells including macrophages, polymorphonuclear cells, NK cells and can be activated under the influence of a simple trauma. Graft rejection is primarily the antigen-specific immune response of the organism, but it is also undoubtedly contributed and enlarged by an inflammatory response.

By all means, there should be no speculation with xenotransplantation, because a number of experiments, giving bad results, are not published or discussed, thus leading to wrong conclusions. We must be very careful when advertising this-or-that in practical medicine, respecting the hopes of million people, who are looking for better issues of their diseases. 

I completely agree with your opinion, I will say later and why, but still need to work on new resources, because obviously these are insufficient for a large number of candidates who are waiting for organ transplants!

I completely agree with your opinion, I will say later and why, but still need to work on new resources, because obviously these are insufficient for a large number of candidates who are waiting for organ transplants!

Perhaps a higher priority should now be given to testing on artificial organs as a potential resource because it avoids biological-immunological barriers or stem cells!