A Heterotopic Mouse Model for Studying Laryngeal Transplantation.

Laryngeal heterotopic transplantation, although a technically challenging procedure, offers more scientific analysis and cost benefits compared to other animal models. Although first described by Shipchandler et al. in 2009, this technique is not widely used, possibly due to the difficulties in learning the microsurgical technique and time required to master it. This paper describes the surgical steps in detail, as well as potential pitfalls to avoid, in order to encourage effective use of this technique. In this model, the bilateral carotid arteries of the donor larynx are anastomosed to the recipient carotid artery and external jugular vein, allowing for blood flow through the graft. Blood flow can be confirmed intraoperatively by the visualization of blood filling in the graft bilateral carotid arteries, reddening of the thyroid glands of the graft, and bleeding from micro vessels in the graft. The crucial elements for success include delicate preservation of the graft vessels, making the correct size arteriotomy and venotomy, and using the appropriate number of sutures on the arterial-arterial and arterial-venous anastomoses to secure vessels without leakage and prevent occlusion. Anyone can become proficient in this model with sufficient training and perform the procedure in approximately 3 h. If performed successfully, this model allows for immunologic studies to be performed with ease and at low cost.

A Heterotopic Rat Heart Transplantation Model using Circulatory Death Donor Hearts.

The objective of this protocol is to set up a rat heterotopic heart transplantation model with donation after circulatory death (DCD) donor hearts. There are two setups for this protocol: heart donor setup and recipient setup. In the heart donor setup, Sprague Dawley rats are anesthetized, endotracheally intubated, and ventilated. The right carotid artery is cannulated to deliver heparin and the paralytic agent vecuronium-bromide. The DCD process is initiated by terminating the ventilation. After 20 min, the heart is exposed and the aorta distal to the brachiocephalic branch is clamped. At 25 min from terminating the ventilator, ice-cold University of Wisconsin (UW) solution is perfused through the carotid catheter to flush the heart. The heart is procured by dividing the aorta, pulmonary artery, venae cavae, and pulmonary veins and stored in UW solution for implantation. In the recipient setup, the Lewis rat is anesthetized with isoflurane. Slow-release buprenorphine is administered subcutaneously to facilitate a smooth postoperative recovery. Through a midline abdominal incision, the infra-renal aorta and the inferior vena cava are isolated and clamped with an atraumatic vascular clamp. The donor heart aorta and pulmonary artery are sutured to the recipient abdominal aorta and vena cava, respectively, with a running 8-0 Prolene. The vascular clamp is removed to reperfuse the heart. The abdominal wall is closed and the rat is recovered. After a set interval (24 h to 2 weeks), the recipient rat is anesthetized, the transplanted heart is exposed, and a balloon-tip-catheter is inserted into the left ventricle via the apex to record developed pressure and dP/dt using a data acquisition system. The heart tissue is collected for histology, immunology, or molecular analysis. A successful DCD donor rat heart transplantation model will allow further studies on the cardioprotective approaches to improve heart transplantation outcomes from DCD donors.

A Modified Cuff Technique for Mouse Cervical Heterotopic Heart Transplantation Model.

Cardiac allograft rejection limits the long-term survival of patients after heart transplantation. A mouse heart transplantation model is ideal for investigating the mechanism of cardiac allograft rejection in preclinical studies because of their high homology with human genes. This understanding would help develop unique approaches to improving patients' long-term survival treated with cardiac allografts. In a mouse model, abdominal donor heart implantation is commonly performed with an end-to-side anastomosis to the recipient's aorta and inferior vena cava using stitches. In this model, the donor's heart is implanted by end-to-end anastomosis to the recipient's carotid artery and jugular vein by the modified-Cuff technique. The transplantation surgery is performed without stitching and thus may increase the survival of the recipient since there is no interference with the blood supply and venous reflux of the lower body. This mouse model would help investigate the mechanisms underlying the immunological and pathological (acute/chronic) rejection of cardiac allografts.

Evaluation of an alternative heterotopic transplantation model for ovarian tissue to test pharmaceuticals improvements for fertility restoration.

BACKGROUND: Ovarian tissue cryopreservation and transplantation (OTCTP) is currently the main option available to preserve fertility in prepubertal patients undergoing aggressive cancer therapy treatments. However, a major limitation of OTCTP is follicle loss after transplantation. The mouse is a model of choice for studying ovarian function and follicle development after ovarian tissue grafting in vivo. In these mouse models, ovarian tissue or ovaries can be transplanted to different sites. Our aim was to evaluate a new alternative to heterotopic transplantation models that could be useful to test pharmaceutical improvement for ovarian grafts after OTCTP. METHODS: Slow frozen murine whole ovaries were transplanted into the mouse ears (between the external ear skin layer and the cartilage). Ovarian transplants were recovered after 3, 14 or 21 days. Grafts were analyzed by immunohistochemistry and follicle density analyses were performed. RESULTS: An increase of ovarian vascularization (CD31 and Dextran-FITC positive staining), as well as cellular proliferation (Ki67 staining) were observed 3 weeks after transplantation in comparison to 3 days. Fibrosis density, evaluated after Van Gieson staining, decreased 3 weeks after transplantation. Furthermore, transplantation of cryopreserved ovaries into ovariectomized mice favored follicle activation compared to transplantation into non-ovariectomized mice. CONCLUSION: The present study indicates that surgical tissue insertion in the highly vascularized murine ear is an effective model for ovarian grafting. This model could be helpful in research to test pharmaceutical strategies to improve the function and survival of cryopreserved and transplanted ovarian tissue.

Neovaginoplasty Using Nile Tilapia Fish Skin as a New Biologic Graft in Patients with Mayer-Rokitansky-Küster-Hauser Syndrome.

Mayer-Rokitansky-Küster-Hauser syndrome is the second most common cause of primary amenorrhea, trailing only to gonadal dysgenesis. Neovaginoplasty is an appropriate treatment option for patients who have failed dilation therapy. Several biomaterials have been used in this procedure, including peritoneum, amnion, skin grafts, and myocutaneous flaps. Nile Tilapia Fish Skin has noninfectious microbiota, morphologic structure comparable to human skin, and high in vivo bioresorption. In addition, it showed good outcomes when used as a xenograft for burn treatment. Thus, we suggest it as a new biologic graft for vaginal agenesis management. In this descriptive study, neovaginoplasty using Nile Tilapia Fish Skin offered 3 patients an anatomic and functional neovagina via a simple method with potential long-term effectiveness. When postsurgical dilation was performed correctly, a vaginal length greater than 6 cm was maintained at 180 days follow-up. Histologic and immunohistochemical analyses revealed the presence of stratified squamous epithelium with high expression of cytokeratins and fibroblast growth factor, matching the characteristics of normal adult vaginal tissue. We believe that further studies will show Nile Tilapia Fish Skin to be a relevant option in the therapeutic arsenal of Mayer-Rokitansky-Küster-Hauser syndrome.

Clinical effect of thumb finger reconstruction using dorsal foot flap transplant for treating thumb defects.

It was found that conventional toe graft alone could not meet the patients' needs for wound repair, so we hypothesized that it would be more effective to treat thumb and finger defect by toe graft with dorsalis foot flap. This prospective study was conducted in 104 thumb defect patients to investigate the clinical effect of thumb reconstruction using toe graft with dorsal foot flap for the treatment of thumb defects. These patients were randomly divided into the dorsal foot group and the control group by randomized double-blind method, with 52 patients in each group. The second toe was used for thumb reconstruction transplant in both the groups. After thumb reconstruction, the abdominal pedicled flap was used to repair the surgical wound in the control group whereas the dorsal foot flap was used to repair the surgical wound in the dorsal foot group. Three months after surgery, the efficacy of surgical treatment, evaluation of two-point discrimination, postoperative complications, function of reconstructed thumb, operation time, and hospitalization time were recorded and compared between the two groups. MHOQ questionnaire was used to evaluate and compare the patients' satisfaction with finger reconstruction in both the groups. The surgical therapeutic effect, the function of the reconstructed thumb, and satisfaction with finger reconstruction were significantly higher in the dorsal foot group compared to the control group (all p < 0.05). The postoperative two-point discrimination, postoperative complication rate, operation time, and hospitalization time of patients in the dorsal foot group were significantly lower compared to the control group (all p < 0.05). Thumb finger reconstruction using the second toe transplant with dorsal foot flap had a beneficial effect on thumb defect patients. It can effectively improve finger function and sensory recovery of patients while reducing complications.

Amniotic membrane, clinical applications and tissue engineering. Review of its ophthalmic use. / Membrana amniótica, aplicaciones clínicas e ingeniería tisular. Revisión de su uso oftalmológico.

The use of amniotic membrane in ophthalmology has been increasing in recent years due to its multiple biological and tectonic properties, improvement in the process of obtaining, ease of use, and advancement in tissue engineering. The amniotic membrane has become one of the main adjuvant treatments, in ophthalmic surgery as well as in other medical-surgical specialties. The development of tissue engineering has allowed it to be used, not only in its classic form, but also by the use of drops and other presentations. The different steps prior to its use (preparation and conservation), the different surgical techniques, and their main clinical applications are described throughout the article.

Murine Cervical Aortic Transplantation Model using a Modified Non-Suture Cuff Technique.

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. However, only minor improvement in the long-term results of transplanted solid organs could be observed over the past decades. In this context, chronic allograft vasculopathy (CAV) still represents the leading cause of late organ failure in cardiac, renal and pulmonary transplantation. Thus far, the underlying pathogenesis of CAV development remains unclear, explaining why effective treatment strategies are presently missing and emphasizing a need for relevant experimental models in order to study the underlying pathophysiology leading to CAV formation. The following protocol describes a murine heterotopic cervical aortic transplantation model using a modified non-suture cuff technique. In this technique, a segment of the thoracic aorta is interpositioned in the right common carotid artery. With the use of the non-suture cuff technique, an easy to learn and reproducible model can be established, minimizing the possible heterogeneity of sutured vascular micro anastomoses.

A case report and follow-up of the first live birth after heterotopic transplantation of cryopreserved ovarian tissue in Eastern Europe.

BACKGROUND: Ovarian insufficiency is a major concern for long-term cancer survivors. Although semen freezing is well established to preserve male fertility, the possibilities to secure post-cancer female fertility are mostly limited to oocyte or embryo freezing. These methods require time-consuming ovarian stimulation with or without in vitro fertilization (IVF) that evidently delays cancer therapy. Ovarian tissue cryopreservation and subsequent thawed tissue autotransplantation are considered the most promising alternative strategy for restoring the fertility of oncology patients, which has not yet received the full clinical acceptance. Therefore, all successful cases are needed to prove its reliability and safety. CASE PRESENTATION: Here we report a single case in Estonia, where a 28-year-old woman with malignant breast neoplasm had ovarian cortex cryopreserved before commencing gonadotoxic chemo- and radiotherapy. Two years after cancer therapy, the patient underwent heterotopic ovarian tissue transplantation into the lateral pelvic wall. The folliculogenesis was stimulated in the transplanted tissue by exogenous follicle-stimulating hormone and oocytes were collected under ultrasound guidance for IVF and embryo transfer. The healthy boy was born after full-term gestation in 2014, first in Eastern Europe. CONCLUSION: Despite many countries have reported the first implementation of the ovarian tissue freezing and transplantation protocols, the data is still limited on the effectiveness of heterotopic ovarian transplant techniques. Thus, all case reports of heterotopic ovarian tissue transplantation and long-term follow-ups to describe the children's health are valuable source of clinical experience.

Temporary ectopic implantation for salvaging amputated parts: A systematic review.

BACKGROUND: Temporary ectopic implantation is an option when handling severe crushing injuries to the distal extremities or other body parts. The surgical techniques applied in those cases, and the patient outcomes have not been previously analyzed. METHODS: Extensive literature search was performed using PubMed, EMBASE, and Google Scholar to collect articles reporting outcomes of temporary ectopic implantation for salvaging amputated extremities or other body parts. Age and sex of patients, injured part, amputation level, surgical details, and clinical outcomes were recorded. RESULTS: Twenty-two articles encompassing 38 amputated cases met the inclusion criteria. The publication dates ranged from 1986 to 2016. Of the 38 cases, temporary ectopic implantation procedures were performed in 16 digit cases, 10 hand cases, 3 forearm cases, 5 foot cases, 1 penis case, 1 testes case, and 2 scalp cases. The ectopic implantation duration varied from 6 to 319 days. The ectopic implantation and following replantation of the amputated parts resulted in a survival rate of 81.6% and 100%, respectively. With different follow-up durations, most patients were found to have sensation restore in the tips of reconstructed extremities, and those reconstructed extremities were functionally useful in daily lives. The function of other replanted parts was also satisfactory. CONCLUSION: Temporary ectopic implantation is a valuable technique for salvaging amputation cases resulted from severe crushing injuries. There is yet no consensus on the indications of this surgical technique. In future practices, both success and failure cases should be recorded and analyzed to help us to optimize the surgical strategies and improve the patient outcomes. LEVEL OF EVIDENCE: Systematic review, level IV.

Transplantation routes affect the efficacy of human umbilical cord mesenchymal stem cells in a rat GDM model.

Gestational diabetes mellitus (GDM) is harmful to both the mother and fetus. Although transplantation of human umbilical cord mesenchymal stem cells (HUMSCs) could be a useful therapy for GDM, the influences of different transplantation routes on the therapeutic effects remain unclear. In this study, we isolated and cultured the HUMSCs for transplantation, and the biological activity of HUMSCs was verified by flow cytometric analysis (the positive markers, CD44, CD73, CD105 and CD90, the negative markers, CD45, CD34, CD19, HLA-DR, and CD11b) and potency of osteogenic, adipogenic and chondrogenic differentiation. Streptozotocin (STZ)-induced diabetes mellitus (DM)/GDM rats were transplanted with HUMSCs by different routes: single or multiple tail vein injection, liver parenchyma, and renal capsule transplantation. These were compared to positive controls (STZ-induced, untreated) and negative controls (non-induced, untreated) to determine the effect of the transplant on the control of DM/GDM. The blood glucose level and body weight of rats in each group were determined and showed different effects. Transplantation of HUMSCs to GDM rats can increase the number of offspring in comparison to the negative controls. The weight of the offspring in the transplantation groups also increased due to the therapeutic effect of HUMSCs. Based on results, we concluded that transplanting HUMSCs could effectively alleviate the symptoms of elevated blood glucose and weight loss and improve the body weight and survival rate of offspring. Injections of HUMSCs were required to persistently decrease the blood glucose of DM and GDM rats. Transplanting HUMSCs into the liver or renal capsule of GDM rats led to a similar efficiency of controlling blood glucose and compensation for body weight. HUMSCs therapy increased the number and body weight of offspring and improved their activity. In summary, this study has enabled progress toward determining the optimal route for GDM therapy.

Experimental Study on the In-Vivo Heterotopic Transplantation of Aortic Valved Homografts after De-Endothelialization.

BACKGROUND AND AIM OF THE STUDY: The study aims were to monitor the changes in tissue morphology, calcium content and CD40 expression in the in-vivo heterotopic transplantation of aortic valved homografts after de-endothelialization, and to seek better methods for preventing calcification and degeneration of the homograft valves. METHODS: Adult, healthy, inbred male Chinese rabbits were used as donors, and inbred adult female New Zealand White rabbits as recipients for the heterotopic transplantation of aortic valved homografts with abdominal aorta. Controls received aortic valved homografts without treatment, while the de-endothelialization group received aortic valved homografts after de-endothelialization. For the cryopreservation group, aortic valved homografts were treated with 10% dimethyl sulfoxide and cryopreserved in liquid nitrogen for 60 days. Recipients were randomly allocated to three groups (n = 20 per group). Grafts were removed after two, four, eight and 12 weeks of surgery and observed with light microscopy. Calcium concentrations were monitored using flame atomic absorption, and CD40 expressions with immunohistochemistry. RESULTS: At two weeks after transplantation, the calcium contents of the fresh, de-endothelialization and cryopreservation groups were similar (p >0.05). The calcium content at four, eight and 12 weeks in the fresh and cryopreservation groups was significantly higher than that in the de-endothelialization group (p <0.01), while at two, four and eight weeks after transplantation, CD40 expression in the fresh and cryopreservation groups was significantly different from that in the de-endothelialization group (p <0.01). CONCLUSION:The calcium content in valve homografts was found to correlate with immune rejection. De-endothelialization could reduce immune rejection reactions and prevent calcification of aortic homograft valve.

[Establishment and comparison of stoma and stoma-free heterotopic small intestine transplantation models in mice].

OBJECTIVE: To establish stoma and stoma-free murine models of heterotopic small intestine transplantation in order to choose a more effective and reliable model. METHODS: A total of 140 male 8-10 weeks age C57BL/6(B6) mice weighted 25-30 g were enrolled in the experiment. Syngeneic heterotopic small intestine transplantation was performed between C57BL/6 mice, and recipient mice were divided into either stoma or stoma-free group. Heterotopic small intestine transplantation was performed in 70 mice, with 35 mice in each group. After closing the proximal end of the graft by ligation, the distal end of graft was exteriorized as a stoma then secured to the skin of the abdominal wall in stoma group. In stoma-free group, the distal end of graft was anastomosed end-to-side to the recipient ileum. Successful rate of operation, two-week survival rate, operation time, associated complications, postoperative care time and body weight change were recorded and compared between two groups. RESULTS: The successful rate of stoma group was 65.7%, while it was 80.0% of stoma-free group (χ(2)=1.806, P=0.179). The operation time of donor in stoma group was (48.1±6.6) minutes, while it was (47.2±5.9) minutes in stoma-free group (t=0.598, P=0.552). The operation time of recipient in stoma group was (77.9±9.1) minutes, while it was (76.4±8.3) minutes in stoma-free group (t=0.683, P=0.497). The cold ischemic time of graft in stoma group was (34.7±4.0) minutes, while it was (33.9±4.6) minutes in stoma-free group(t=0.667, P=0.507). The two-week survival rate of stoma group was 45.7%, and it was 77.1% of stoma-free group(χ(2)=7.295, P=0.007). The stoma group had more complications[54.3%(19/35) vs. 22.9%(8/35), χ(2)=7.295, P=0.007], which needed more postoperative care time(191 min vs. 35 min). The weight loss in stoma group in the third day after operation was more significant [(81.52±5.20)% vs. (85.46±4.65)%, t=2.856, P=0.006]. By 2 weeks after operation, the weight of mice in both groups retruned to 95% of the postoperative wight. CONCLUSION: The murine heteropotic small intestine transplantation model with stoma-free appears to be more reasonable and reliable.

A Comparison between splenic fossa and subhepatic fossa auxiliary partial heterotopic liver transplantation in a porcine model.

To test the alternative possible locations for the placement of a liver graft and the relevant surgical technique issues, we developed a porcine model of auxiliary partial heterotopic liver transplantation (APHLT) and evaluated the difference between 2 styles of liver transplantation, either subhepatic fossa or splenic fossa APHLT, by comparing survival and biochemical indexes. Thirty-eight miniature pigs were randomly divided into 2 groups. A left hemihepatic graft without the middle hepatic vein (HV) was procured from the living donor. In group A (n = 9), an 8 mm diameter polytetrafluoroethylene (PTFE) graft approximately 2.5 cm long was connected to the left HV while another PTFE graft of the same size was connected to the left portal vein (PV). The liver graft was implanted in the right subhepatic fossa following splenectomy and right nephrectomy. In group B (n = 10), a PTFE graft of the same size was connected to the left HV while the liver graft was implanted in the splenic fossa following splenectomy and left nephrectomy. Survival rate and complications were observed at 2 weeks after transplantation. Data were collected from 5 animals in group A and 6 animals in group B that survived longer than 2 weeks. The liver function and renal function of the recipients returned to normal at 1 week after surgery in both groups. Eighty-eight percent (14/16) of the PTFE grafts remained patent at 2 weeks after surgery, but 44% of the PTFE grafts (7/16) developed mural thrombus. No significant differences in the survival rate and biochemistry were found between the 2 groups. In conclusion, the splenic fossa APHLT can achieve beneficial outcomes similar to the subhepatic fossa APHLT in miniature pigs, although it also has a high morbidity rate due to hepatic artery thrombosis, PV thrombosis, and PTEF graft mural thrombus formation. Liver Transplantation 22 812-821 2016 AASLD.

Heterotopic Vascularized Joint Transfer in Mutilating Hand Injuries.

BACKGROUND: In cases of mutilating hand injuries, the primary goal is recovery of prehensile function. This is particularly true in the case of joints, which are extremely difficult to replace or reconstruct adequately when damaged. Heterotopic vascularized joint transfer is indicated when salvageable joints are available for transfer to a more functionally optimal position on the hand. MATERIALS AND METHODS: Seven cases of mutilating hand injuries treated with heterotopic vascularized joint transfers from 2003 to 2012 were retrospectively identified. All patients sustained severe metacarpophalangeal joint (MPJ) or proximal interphalangeal joint (PIPJ) damage that threatened recovery of optimal hand function. All patients were men, with an average age of 34.7 years. Operative, perioperative, and postoperative details including final active range of motion were collected and analyzed. RESULTS: Seven joints were taken from nonsalvageable amputated digits: 4 from the amputated parts, and 3 from the proximal stumps. Five joints were transferred as free flaps requiring microvascular anastomosis, and 2 were transferred on neurovascular pedicles. One joint was lost due to vasospasm. Average active range of motion was 68.3° for homojoint transfers (MPJ to MPJ, PIPJ to PIPJ), and 35° for heterojoint transfers. All but 1 patient were able to achieve tripod pinch; the remaining patient achieved only side-to-side pinch. CONCLUSIONS: Heterotopic vascularized joint transfer is a useful technique to consider in cases of mutilating hand injuries. Improved recovery of prehensile function can be achieved with thoughtful design and execution, followed by proper patient education and rehabilitation.

From baby to man with a piggyback heart: long-term success of heterotopic heart transplantation.

We present a case of a young man, who underwent heterotopic heart transplantation 20 years ago, when he was 6 months old. The baby suffered from severe intractable cardiomyopathy. In this desperate situation only a miniature, compromised donor heart became available. Today, the young man is fully active under minimal immunosuppression. His surgical course is reviewed and described.

Synergistic Effects of Combined Cell Therapy for Chronic Ischemic Cardiomyopathy.

BACKGROUND: Both bone marrow-derived mesenchymal stem cells (MSCs) and c-kit(+) cardiac stem cells (CSCs) improve left ventricular remodeling in porcine models and clinical trials. Using xenogeneic (human) cells in immunosuppressed animals with acute ischemic heart disease, we previously showed that these 2 cell types act synergistically. OBJECTIVES: To more accurately model clinical applications for heart failure, this study tested whether the combination of autologous MSCs and CSCs produce greater improvement in cardiac performance than MSCs alone in a nonimmunosuppressed porcine model of chronic ischemic cardiomyopathy. METHODS: Three months after ischemia/reperfusion injury, Göttingen swine received transendocardial injections with MSCs alone (n = 6) or in combination with cardiac-derived CSCs (n = 8), or placebo (vehicle; n = 6). Cardiac functional and anatomic parameters were assessed using cardiac magnetic resonance at baseline and before and after therapy. RESULTS: Both groups of cell-treated animals exhibited significantly reduced scar size (MSCs -44.1 ± 6.8%; CSC/MSC -37.2 ± 5.4%; placebo -12.9 ± 4.2%; p < 0.0001), increased viable tissue, and improved wall motion relative to placebo 3 months post-injection. Ejection fraction (EF) improved (MSCs 2.9 ± 1.6 EF units; CSC/MSC 6.9 ± 2.8 EF units; placebo 2.5 ± 1.6 EF units; p = 0.0009), as did stroke volume, cardiac output, and diastolic strain only in the combination-treated animals, which also exhibited increased cardiomyocyte mitotic activity. CONCLUSIONS: These findings illustrate that interactions between MSCs and CSCs enhance cardiac performance more than MSCs alone, establish the safety of autologous cell combination strategies, and support the development of second-generation cell therapeutic products.

Single-port laparoscopic ovarian transposition in an 11-year-old girl.

Ovarian transposition was the first procedure proposed for children with cancer to preserve ovarian function from damage caused by abdominal and pelvic radiotherapy. In this paper, we describe the first pediatric case of single-port laparoscopic ovarian transposition.

Pharmacological strategies for protection of extrahepatic islet transplantation.

The safety and effectiveness of islet transplantation has been proven through world-wide trials. However, acute and chronic islet loss has hindered the ultimate objective of becoming a widely used treatment option for type 1 diabetes. A large islet loss is attributed, in part, to the liver being a less-than-optimal site for transplantation. Over half of the transplanted islets are destroyed shortly after transplantation due to direct exposure to blood and non-specific inflammation. Successfully engrafted islets are continuously exposed to the liver micro-environment, a unique immune system, low oxygen tension, toxins and high glucose, which is toxic to islets, leading to premature islet dysfunction/death. Investigations have continued to search for alternate sites to transplant islets that provide a better environment for prolonged function and survival. This article gathers courses and conditions that lead to islet loss, from organ procurement through islet transplantation, with special emphasis on hypoxia, oxidative stress, and antigen non-specific inflammation, and reviews strategies using pharmacological agents that have shown effectiveness in protecting islets, including a new treatment approach utilizing siRNA. Pharmacological agents that support islet survival and promote ß-cell proliferation are also included. Treatment of donor pancreata and/or islets with these agents should increase the effectiveness of islets transplanted into extrahepatic sites. Furthermore, the development of methods designed to release these agents over an extended period, will further increase their efficacy. This requires the combined efforts of both islet transplant biologists and bioengineers.

A gastrocnemius heterotopical transplant model with end-to-side neurorraphy.

PURPOSE: To present an animal model to assess the effects of end-to-side innervation in the heterotopically transplanted model with reduced chances of neural contamination. METHODS: The medial portion of the gastrocnemius muscle in wistar male rats was isolated and its pedicle dissected and performed a flap in the abdominal portion. To prevent neural contamination in the abdominal region, the muscle was wrapped with a Goretex(r) sheet. The specimens were divided into 2 groups (G). In G1 was performed an end-to-end suture between tibial nerve of the gastrocnemius and femoral motor nerve and between the saphenous sensory nerve and the motor nerve. In G2 was performed a end-to-side suture between the tibial nerve and the motor femoral and between the tibial nerve and saphenous motor nerve. The specimens were evaluated 60 days later to check the structure of the neurorraphy. Sections were obtained proximal and distal to the coaptation site. RESULTS: The medial gastrocnemius muscle had the advantage of maintaining visible mass after 60 days. No disruption of the coaptation site was found. No major injury to the donor nerve was seen in group 2. CONCLUSION: The proposed model is simple, reproduciple and prevent the neural contamination in the flap in end-to-side suture.