Solid organ xenotransplantation using transgenic pig organs is proposed as an alternative method for allo-transplantation. To accomplish this, immunologic and non-immunologic barriers for xenotransplantation should be overcome, and experiments on pigs to non-human primates (NHP) are now ongoing for clinical application. Before the clinical experiment, public consensus about ethical decisions must be considered. The results of NHP experiments on solid organ xenotransplantation are improving, and it is expected that xeno-solid organs can be used as new organs for human patients in the future.
Consensus ; Humans ; Methods ; Primates ; Swine ; Transplantation, Heterologous*

Bone xenograft bone for the treatment of bone defect is one of the current research focus, which has advantages of extensive sources, low cost, simple preparation method. While the process of single bone xenograft bone in repairing bone defect is very long, and the clinical outcome is not satisfactory. The main problems focus on formation of bone and vascularization. Reconstituted bone xenograft combined with cells and xenogenic bone material could promote vascularization and bone fusion in vivo, thus achieve a clinical effect of autogenous bone in repairing bone defect.
Bone Transplantation ; methods ; Bone and Bones ; blood supply ; Humans ; Transplantation, Heterologous

OBJECTIVETo prepare a porcine acellular dermal matrix (PADM), and to optimize the interpore distance between PADM and co-grafted split-thickness autologous skin.

METHODSPorcine skin was treated with trypsin/Triton X-100 to prepare an acellular dermal matrix. Micropores were produced on the PADM with a laser punch. The distance between micropores varied as 0.8 mm, 1.0 mm, 1.2 mm and 1.5 mm. Full-thickness defect wounds were created on the back of 144 SD rats. The rats were randomly divided into 6 groups as follows, with 24 rats in each group. Micropore groups I -IV: the wounds were grafted with PADM with micropores in four different intervals respectively, and covered with split-thickness autologous skin graft. Mesh group: the wounds were grafted with meshed PADM and split-thickness autograft.

CONTROL GROUPwith simple split-thickness autografting. The gross observation of wound healing and histological observation were performed at 2, 4, 6 weeks after surgery. The wound healing rate and contraction rate were calculated.

RESULTSTwo and four weeks after surgery, the wound healing rate in micropore groups I and II was lower than that in control group (P < 0.05), but no obvious difference was between micropore groups I , II and mesh group (P > 0.05) until 6 weeks after grafting( P <0.05). The wound contraction rate in micropore groups I and II ([(16.0 +/- 2.6)%, (15.1 +/- 2.4)%] was remarkably lower than that in control group 4 and 6 weeks after grafting (P < 0.05), and it was significantly lower than that in mesh group [(19.3 +/- 2.4)%] 6 weeks after surgery (P <0.05). Histological examination showed good epithelization, regularly arranged collagenous fibers, and integral structure of basement membrane.

CONCLUSIONLaser micropore PADM (0.8 mm or 1.0 mm in distance) grafting in combination with split-thickness autografting can improve the quality of wound healing. PADM with laser micropores in 1.0 mm distance is the best choice among them.

Animals ; Dermis ; transplantation ; Lasers ; Rats ; Rats, Sprague-Dawley ; Skin Transplantation ; methods ; Skin, Artificial ; Swine ; 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

In this study the treatment effect of combined implantation of autologous skin on pig dermis in injured rats was observed. Twenty-one Wistar rats were used, and the wounds were formed by excising a piece of full thickness skin on the back. After the pig dermis was implanted, the autologous skin was grafted on the dermis at 0.7 and 10 days. In the group with perforated pig dermis, the autograft skin was implanted on the day when the pig dermis was implanted. The healing effect was evaluated by measuring wound area, and by observing the growth of the autograft skin. Two weeks after the autograft skin was implanted, the skin securely adhered to the dermis, and the edge of autograft skin expanded clearly. The wound of the autograft skin implanted in the perforation of the dermis healed completely after 3 weeks, but the other 3 groups had remnant small wound. The autograft skin merged with the dermis and its surrounding tissue, but a clear dividing line still existed between autograft skin and dermis after implantation. The area of the implanted dermis and autograft skin varied from 51.8% to 65.9% compared to its original size. The results suggested that the time and the way of autologous skin grafting on xenogenous dermis may influence wound contraction and healing time.
Animals ; Dermis ; transplantation ; Female ; Graft Survival ; Male ; Rats ; Rats, Wistar ; Skin Transplantation ; methods ; Swine ; Swine, Miniature ; Transplantation, Autologous ; 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

The purpose of this study was to estimate the possibilities of an acellular matrix using a modified acellularization protocol, which circumvents immunological, microbiological, and physiological barriers. We treated porcine subclavian arteries with various reagents to construct acellular grafts. Afterwards, these grafts were interposed in a mongrel dogs' abdominal aorta. Six dogs underwent interposition with fresh porcine grafts (control group), and seven had interposed acellular grafts (acellular group). The control and acellular group dogs were sacrificed at 1, 3, 5 (n=2 in each group) and 12 months (n=1 in acellular group) after the operation. Histopathological examinations were then performed, to assess the degree to which re-endothelialization, inflammation, thrombus formation, and calcification occurred. The entire acellular group, but none of the control group, exhibited re-endothelialization. The degrees to which inflammation, thrombosis, and calcification occurred were found to be lower in the acellular group. We also discovered many smooth muscle cells in the medial layer of the xenograft that had been implanted in the dog sacrificed 12 months after the operation. These results suggest that the construction of xenografts using our modified acellularization protocol may offer acceptable outcomes as a vascular xenograft.
Transplantation, Heterologous/*methods ; Tissue Engineering/*methods ; Swine ; Subclavian Artery/*cytology/*transplantation ; Graft Survival/*physiology ; Dogs ; Cell-Free System/*transplantation ; Animals

OBJECTIVETo provide experimental evidence for the feasibility of repair of deep partial thickness burn wounds with autologous skin grafting on retained denatured dermis.

METHODSDeep partial thickness burn wounds 3.5 cm x 3.5 cm in size were produced on the back of SD rats. Superficial tangential excision was performed on the burn wounds on 2 - 5 postburn days with the preservation of denatured dermis. Split thickness autoskin was grafted on the wounds immediately. Tissue samples of whole layer of the skin were harvested from the grafted sites at different time points after the skin grafting, with 8 rats in each group. The morphology and the changes in the collagen fibres in the above tissue samples were observed by light microscopy (LM) and the changes in the biodynamics were determined. The normal skin from the same rat receiving skin grafting was employed as the control.

RESULTS(1) Vitreous degeneration was observed in the preserved denatured dermis. (2) The grafted skin was fused to the burn wound on the 7th day after autoskin grafting in rats. The dermal papillae and reticular layer could be discernible under LM. The thickness, structure and morphology of the skin on the grafted area were similar to normal tissue on the 21st day after grafting with atrophic hair follicles. The density of collagen fiber cord increased gradually, and almost fused at last. (3) The tensile strength, and maximum strain value of the rat skin after operation increased gradually, approaching normal on 60 post-operational day.

CONCLUSIONThe denatured dermis can recover gradually with normal structure and morphology after the application of autoskin on it for the repair of deep partial thickness burn wounds.

Animals ; Burns ; surgery ; Dermis ; pathology ; transplantation ; Graft Survival ; Rats ; Rats, Sprague-Dawley ; Skin Transplantation ; methods ; Transplantation, Heterologous ; Wound Healing

OBJECTIVETo explore the feasibility of application of xenoskin as microskin graft covering.

METHODSTen patients with deep and extensive burns were enrolled in the study. A white pig weighing about 50kg was cleaned and shaved(without boiled water treatment) after being slaughtered. After conventional disinfection, two pieces of skin with little amount of fat were removed from the pig and processed to full-thickness or split-thickness skin. Before operation they were perforated and autogeneic microskin was scattered onto it. After escharectomy they were grafted on the wound, and the wound was dressed and bandaged with pressure. The rejection of the xenoskin, the survival of the microskin grafts, the wound healing time,and the functional recovery of the patients 1 year after operation were observed.

RESULTSThe porcine skin was intact, and stuck well to the wound within 2 post-operation weeks ( POW). But it turned to form a dry scab, and gradually separated from the autogeneic microskin during 4 - 5 POW. The xenoskin completely fell off and the wound healed during 6 - 8 POW . The wound healing time of the 10 patients was 42 - 56 days [ (50 +/- 5) d]. Though there were thin scars 1 year after operation, the elasticity and function of the skin were normal.

CONCLUSIONIt is feasible to use porcine skin as a substitute of alloskin to cover autogenous microskin.

Adult ; Animals ; Burns ; surgery ; Feasibility Studies ; Female ; Graft Survival ; Humans ; Male ; Skin Transplantation ; 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