Skin grafting has been one of the most important approaches for covering burn wounds, however long-term survival of allogeneic or xenogeneic skin graft is currently not successful. How to induce immune tolerance for life-time survival of allogeneic or xenogeneic skin graft is still remote objective to be solved. However, clinicians and scientists in China have worked very hard and made great contribution to this field during the past 50 years, no matter how difficult it is. They are the respected pioneers in the understanding of immunological change in "Chinese Method" skin grafting, its local immune tolerance, immunology of pre-treatment of skin graft, etc. Herein, the most outstanding and impressive progresses in immunological responses after skin grafting in the past 50 years in China have been reviewed and presented for memory, for future and for extending a salute.
Humans ; Immune Tolerance ; Skin Transplantation ; immunology ; Transplantation, Heterologous ; immunology ; Transplantation, Homologous ; immunology

α-Gal, the main xenotransplantation antigen, can lead to hyperacute rejection (HAR) in xenotransplantation. This study was purposed to investigate the effect of recombinant α-galactosidase (α-Gal antigen) on the Holstein-Friesian(H-F) red blood cells (RBC). The enzymelysis method was used to digest the α-Gal antigen on H-F RBC; the saline and anti-human globulin methods were used to perform the agglutination test of H-F RBC and human plasma; the flow cytometry was used to detect the α-Gal antigen on surface of H-F RBC, fluorescence intensity of FITC-IB4 and FITC-IgG labeled RBC. The results indicated that the saline and anti-human globulin method showed α-galactosidase-treated H-F RBC fail to agglutinate with human pooled plasma; the flow cytometry showed the fluorescence intensity of FITC-IB4 and FITC-IgG labeled RBC decrease 99.0% and 87.8%, respectively. It is concluded that the novel α-galactosidase can be used to cleared the α-Gal antigen on the surface of H-F RBC and α-galactosidase-treated H-F RBC may be considered as human blood substitute.
Animals ; Blood Substitutes ; Cattle ; Erythrocytes ; immunology ; Female ; Humans ; Transplantation, Heterologous

OBJECTIVETo review the current status and progress on pig islet xenotransplantation.

DATA SOURCESData used in this review were mainly from English literature of Pubmed database. The search terms were "pig islet" and "xenotransplantation".

STUDY SELECTIONThe original articles and critical reviews selected were relevant to this review's theme.

RESULTSPigs are suggested to be an ideal candidate for obtaining available islet cells for transplantation. However, the potential clinical application of pig islet is still facing challenges including inadequate yield of high-quality functional islets and xenorejection of the transplants. The former can be overcome mainly by selection of a suitable pathogen-free source herd and the development of isolation and purification technology. While the feasibility of successful preclinical pig islet xenotranplantation provides insights in the possible mechanisms of xenogeneic immune recognition and rejection to overwhelm the latter. In addition, the achievement of long-term insulin independence in diabetic models by means of distinct islet products and novel immunotherapeutic strategies is promising.

CONCLUSIONSPig islet xenotransplantation is one of the prospective treatments to bridge the gap between the needs of transplantation in patients with diabetes and available islet cells. Nonetheless, further studies and efforts are needed to translate obtained findings into tangible applications.

Animals ; Graft Rejection ; immunology ; prevention & control ; Islets of Langerhans Transplantation ; immunology ; methods ; Swine ; Transplantation, Heterologous ; methods

Advances in the field of xenotransplantation raise the intriguing possibility of using porcine red blood cells (pRBCs) as an alternative source for blood transfusion. Serologically, pRBCs share a number of characteristics with human red blood cells (RBCs), so pRBCs are considered the most likely donor for xenotransfusion. However, xenoantigens on porcine erythrocytes play major roles in antibody-mediated RBC destruction. Although the alphaGal epitope (Galalpha1, 3Galbeta1, 4GalNAc-R) is the major xenoantigen on porcine erythrocytes and is responsible for the binding of the majority of human natural antibodies, other non-alphaGal xenoantigens have been identified. The importance of these non-alphaGal xenoantigens in binding human natural antibodies and subsequently triggering immunological responses cannot be underestimated.
Animals ; Blood Group Antigens ; immunology ; Erythrocyte Transfusion ; methods ; Erythrocytes ; cytology ; immunology ; Humans ; Swine ; Transplantation, Heterologous ; immunology

OBJECTIVETo investigate the difference of the antigenicity of xenogenic acellular dermal matrix (ADM) implants prepared by different methods.

METHODSThe split-thickness skin sheet from swine was processed by trypsin and Triton X-100 to make xeno-ADM. Twenty-five Japanese white rabbits were divided into 5 groups, i.e. xeno-ADM(1) (conjugated with glutaraldehyde), xeno-ADM(2) (conjugated with network) and xeno-ADM(3) (no conjugation, as control), in which the ADMs were and xeno-ADM(4) (conjugated) and allo-ADM (no conjugated as control), in which the ADMs were embedded into the subcutaneous place of rabbit ear and back after that the rabbits were pre-sensitized by xeno-ADM soluble protein antigen injections. The titers of anti ADMs antibody in rabbit serum were monitored during 2 - 32 post-operative weeks and the histological changes of the embedded ADMs were observed grossly and microscopically.

RESULTSThe serum titers of anti-xeno-ADM in xeno-ADM(4) group was the highest. Whereas regardless of the sensitizing effects, the titers in all groups ranged as follows: xeno-ADM(3) > xeno-ADM(2) > xeno-ADM(1) (P < 0.05 - 0.01). About 40% serum samples in allo-ADM group exhibited positive anti-allo-ADM protein antibodies. Histologically, Evident and lasting inflammatory reaction could be found in the xeno-ADM grafting sites, which was much stronger than that in allo-ADM group. The degradation and absorption gradient of ADM was ranked as follow: xeno-ADM(3) > xeno-ADM(2) > xeno-ADM(4) > xeno-ADM(1) > Allo-ADM. Foreign body megalocytic reaction might evoke in the surrounding of conjugated ADM.

CONCLUSIONThe immunogenicity in xeno-ADM was stronger than that in allo-ADM, which could induce the host to develop immune reaction restricted by IgG. Large sheets of degenerated ADM implants could lower down the antigen-antibody reaction and ameliorate the structural destroying and degeneration absorption of ADM induced by inflammatory immune reaction.

Animals ; Antigen-Antibody Reactions ; Dermis ; immunology ; transplantation ; Male ; Rabbits ; Skin Transplantation ; Swine ; Transplantation, Heterologous

OBJECTIVETo investigate the immunologic reaction difference between xenogeneic and allogeneic acellular dermal matrix (ADM) grafting.

METHODSSplit thick skin samples harvested from healthy piglets and human volunteers who underwent losing-weight operation were processed to be xeno-ADM and allo-ADM. The ADMs overlapped with ultrathin auto-skin were employed to immediately cover the wound after escharectomy in deep burn patients. The patients were correspondingly set to be Xeno (26 cases) and Allo (10 cases) groups. Another 8 cases with deep burn wounds were grafted with only split thick autoskin (TTS) after escharectomy as control group. The tissue samples from grafted area were observed by immunohistochemistry after the grafting. The typing of immune cells in peripheral blood and grafted tissue was determined.

RESULTS(1) The CD4(+), CD45RO(+) and CD4(+)/CD8(+) cell ratios in peripheral blood in Xeno group increased slightly after the skin grafting when comparing to those in control group (P > 0.05). (2) There existed lasting inflammatory and immunological reaction in the local site of grafts in Xeno group. In addition, more than 80% of the inflammatory cells could be found to be CD3(+)/CD4(+), CD45RO(+). But CD8(+), Vs8C(+) plasmocytes and CD57(+) NK cells were found less. Furthermore, eosinophil and CD68(+)/CD4(+) foreign body megalocyte reactions could also be identified, especially in Xeno-ADM before rejection (P < 0.05 - 0.001). There was only mild inflammatory and immunological reaction during early grafting stage (within 8 post-operational weeks) in Allo-group.

CONCLUSIONThe specific immunologic reaction of human host to ADM might be participated by mononuclear cells and macrophages and presented mainly as cellular immune reaction induced by CD4(+) T lymphocytes. Furthermore, the foreign body megalocyte constructed by help T cell and macrophage might play important roles in the reaction.

Animals ; Burns ; immunology ; surgery ; Dermis ; transplantation ; Graft Rejection ; Humans ; Skin Transplantation ; immunology ; methods ; Swine ; Transplantation, Heterologous ; Transplantation, Homologous

Microencapsulation of cells or tissue fragments represents a potentially effective method to prevent graft rejection in allotransplantation and xenotransplantation without the need of immunosuppression, but the functional survival of all trial grafts is still limited. Usually, graft failure is mainly interpreted as the consequence of the progressive fibrotic overgrowth of capsules, the insufficient supply of oxygen and nutrition to the encapsulated graft, and the dysfunction of the encapsulated graft induced by small proinflammatory factors. These detrimental factors are interrelatd with the microcapsules, the implanted graft, and the transplantation site. This article reviews and summarizes the advance and the limitation of microencapsulated grafts transplantation in the above-mentioned aspects.
Alginates ; chemistry ; Animals ; Biocompatible Materials ; chemistry ; Capsules ; Graft Survival ; immunology ; Humans ; Islets of Langerhans Transplantation ; immunology ; methods ; physiology ; Transplantation, Heterologous ; immunology

OBJECTIVETo observe the immune response after the transplantation of a deproteinized heterogeneous bone scaffold and provides the theoretic reference for clinical practice.

METHODSThe fresh pig bone and deproteinized bone were transplanted respectively to establish BABL/C thigh muscle pouches model of male mice and take the samples for detection at 1, 2, 4, 6 weeks after operation. Lymphocyte stimulation index, subset analysis, serum specific antibody IgG, cytokine detection and topographic histologic reaction after implantation were investigated.

RESULTSAfter the transplantation of deproteinized bone, lymphocyte stimulation index, CD(4)(+) and CD(8)(+) T-lymphocyte subsets, serum specific antibody IgG and cytokines in deproteinized bone group were significantly lower than those in fresh pig bone group at each time point (P<0.05). The histological examination found that in fresh bone group at each time point, a large quantity of inflammatory cells infiltrated in the surrounding of bone graft, and they were mainly lymphocytes, including macrophages and monocytes. In deproteinized bone group, there were few inflammatory cells infiltration around bone graft one week after operation. The lymphocytes were decreased as time went by. At 6 weeks, fibroblasts and fibrous tissue grew into the graft, and osteoclasts and osteoprogenitor cells appeared on the verge.

CONCLUSIONSThe established heterogeneous deproteinized bone has low immunogenicity and is a potentially ideal scaffold material for bone tissue engineering.

Animals ; Bone Transplantation ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Swine ; Tissue Engineering ; methods ; Tissue Scaffolds ; Transplantation, Heterologous

Since Nature published the first report in 2002 on using immunodeficient mice as recipients and allogeneous or heterogeneous testes as donor tissues to study the ectopic development of spermatogenic cells, the technique has been widely applied in various species (including human). In comparison with other in vitro maturation methods for male germ cells, testicular allografting or xenografting technique has such advantages as similar environment for the development of germ cells in physiological conditions, and better reproducibility. Up to now, sperm has been successfully produced by this technique from the testicular tisues of the immature mouse, hamster, cat, rabbit, pig, goat, bovine and rhesus monkey, and their offspring have even been generated by ICSI technique using the mouse and rabbit sperm derived from testis grafts. This article comprehensively reviews the development of the technique by discussing the influencing factors on the germ cell development in grafts including the variety and age of donors, the sex, integrity and immunity of recipients, the graft location and grafting time. And the applications of the technique and the existing problems are discussed as well.
Animals ; Cats ; Cattle ; Cricetinae ; Goats ; Humans ; Macaca mulatta ; Male ; Mice ; Rabbits ; Swine ; Testis ; transplantation ; Transplantation Immunology ; Transplantation, Heterologous ; Transplantation, Heterotopic ; Transplantation, Homologous

A heterologous corneal endothelial transplantation was attempted using human endothelial cells and a Lewis rat penetrating keratoplasty model. Cultured human endothelial cells were seeded to a Lewis rat cornea, which was denuded of its endothelium. When grafted into the syngeneic Lewis rat, the graft remained clear for at least five days, and then became opaque and edematous because of immune rejection reaction. In contrast, corneas denuded of their endothelium became opaque and edematous immediately after transplantation. These results demonstrate that transplanted endothelial cells have enough antigens to induce rejection reaction even though they have the functional capacity to deturge the cornea.
Animals ; Endothelium, Corneal/cytology/immunology/*transplantation ; Female ; Graft Rejection/*immunology ; Humans ; Major Histocompatibility Complex/immunology ; Rats ; Rats, Inbred Lew ; Transplantation, Heterologous