Therapeutic effect of adipose-derived mesenchymal stem cells in a porcine model of abdominal sepsis.

BACKGROUND: The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis. METHODS: We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 106 cells/kg or 4 × 106 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity. RESULTS: One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-ß in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity. CONCLUSIONS: Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.

Starting a new program of split liver transplantation after a low learning curve: a reality in centers with large experience in liver surgery and whole liver transplantation.

BACKGROUND/AIMS: Split liver transplantation (SLT) is nowadays, considered an adequate surgical solution to expand the grafts from the existing pool of cadaveric donors. METHODOLOGY: A total of 897 liver transplantations were performed between 1986 and 2002; 20 were SLTs (2.3%). A 30% were children. RESULTS: Mean follow up of 15.15 months +/- 13.85. Median age was 42.27 +/- 25.65 yrs. Median recipient weight was 52.29 +/- 20.87 Kg. Mean donor weight was 76.1 +/- 13.11. The majority was "in situ" SLT (65%). There was no primary graft dysfunction. Two patients developed biliary complications (none in situ SLT). Early HAT occurred in 2 patients and delayed HAT in one. Four patients were retransplanted but none were performed because of primary graft dysfunction. Five patients died in the hospital. Fifteen patients (75%) survived the postoperative period and 3 patients died during follow-up. Mean patient survival time was 42 months (95% CI: 31-52). Actuarial patient survival was 93.3%, 84.4%, 84.4% at 6 months, 1 year and 3 years. Mean graft survival was 36 months (95% CI: 25-48). Actuarial graft survival was 87%, 72%, 72% at 6, 12, 36 months. Univariate analysis of risk factors for graft loss showed that the type of splitting technique (p=0.019), and the UNOS (1 and 2a) status of the recipient (p=0.001) were significantly associated with graft loss. CONCLUSIONS: In the context of large volume full cadaveric liver transplantation, split liver can provide adequate results (even after a short learning curve) mainly in elective cases and with the in situ technique.

First Spanish series of intestinal transplantation in adult recipients.

BACKGROUND: short-bowel transplantation has experienced a substantial growth worldwide following improved results from the late 1990's on, and its coverage by Medicare. According to the International Registry (1985-2005), a total of 1,292 intestinal transplants for 1,210 patients in 65 hospitals across 20 countries have been carried out thus far. OBJECTIVE: to know short-term (6 months) results regarding patient and graft survival from the first Spanish series of intestinal transplants in adult recipients. MATERIAL AND METHODS: we present our experience in the assessment of 20 potential candidates to short-bowel transplantation between June 2004 and October 2005. Of these, 10 patients were rejected and 4 were transplanted, which makes up the sample of our study. RESULTS: to this date 5 transplants have been carried out in 4 patients (2 retransplants, 2 desmoid tumors, 1 short bowel syndrome after excision as a result of mesenteric ischemia). Upon study completion and after a mean follow-up of 180 days (range 90-190 days) all recipients are alive, and all grafts but one (75%) are fully operational, with complete digestive autonomy. All patients received induction with alemtuzumab except one, who received thymoglobulin; in all induction was initiated with no steroids. CONCLUSIONS: intestinal transplantation represents a therapeutic option that is applicable in our setting and valid for recipients with an indication who have no other feasible alternative to keep their intestinal failure under control.

Primera serie nacional de trasplante de intestino en receptores adultos / First Spanish series of intestinal transplantation in adult recipients

Introducción: el trasplante de intestino, con la mejoría en los resultadosdesde finales de los años 90 y desde su cobertura por el Medicare,ha experimentado un crecimiento sustancial a nivel internacional.En la actualidad, según el Registro Internacional (1985-2005),se han realizado un total de 1.292 trasplantes de intestino en 1.210pacientes en 65 hospitales distribuidos por 20 países.Objetivo: conocer los resultados a corto plazo (6 meses) entérminos de supervivencia del paciente y del injerto de la primeraserie nacional de trasplante de intestino en receptores adultos.Material y métodos: presentamos nuestra experiencia en laevaluación de 20 potenciales candidatos a trasplante intestinal entrejunio de 2004 y octubre de 2005. De ellos, fueron desestimadosun total 10 pacientes y fueron trasplantados 4, lo que constituyela muestra de nuestro estudio.Resultados: hasta la fecha se han realizado 5 trasplantes en 4pacientes (2 retrasplantes, 2 tumores desmoides, y 1 síndrome deintestino corto tras exéresis por isquemia mesentérica). Al final delestudio y tras un seguimiento medio de 180 días (rango, 90-190días), todos los receptores están vivos, y todos los injertos, a excepciónde uno (75%), están funcionando plenamente, con autonomíadigestiva completa. Todos los pacientes recibieron induccióncon alemtuzumab excepto uno que recibió timoglobulina y entodos se inició la inducción sin esteroides.Conclusiones: el trasplante intestinal constituye una opciónterapéutica aplicable en nuestro medio y válida en receptores enquienes está indicado y que no tienen otra alternativa válida paracontrolar su insuficiencia intestinal

Background: short-bowel transplantation has experienced asubstantial growth worldwide following improved results from thelate 1990s on, and its coverage by Medicare. According to the InternationalRegistry (1985-2005), a total of 1,292 intestinal trasplantsfor 1,210 patients in 65 hospitals across 20 countries have been carriedout thus far.Objective: to know short-term (6 months) results regardingpatient and graft survival from the first Spanish series of intestinaltransplants in adult recipients.Material and methods: we present our experience in the assessmentof 20 potential candidates to short-bowel transplantationbetween June 2004 and October 2005. Of these, 10 patientswere rejected and 4 were transplanted, which makes up thesample of our study.Results: to this date 5 transplants have been carried out in4 patients (2 retransplants, 2 desmoid tumors, 1 short bowelsyndrome after excision as a result of mesenteric ischemia).Upon study completion and after a mean follow-up of 180days (range 90-190 days) all recipients are alive, and all graftsbut one (75%) are fully operational, with complete digestiveautonomy. All patients received induction with alemtuzumabexcept one, who received thymoglobulin; in all induction wasinitiated with no steroids.Conclusions: intestinal transplantation represents a therapeuticoption that is applicable in our setting and valid for recipientswith an indication who have no other feasible alternative tokeep their intestinal failure under control