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Small intestine and tissue engineering: challenges of regenerative medicine

Grant number: 13/19940-3
Support type:Regular Research Grants
Duration: August 01, 2014 - July 31, 2016
Field of knowledge:Interdisciplinary Subjects
Principal Investigator:Alexandre Bakonyi Neto
Grantee:Alexandre Bakonyi Neto
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Assoc. researchers:Carla Adriene da Silva Franchi ; Elenice Deffune ; Maria Aparecida Marchesan Rodrigues Kobayasi

Abstract

Short bowel syndrome is a condition in which there is insufficient intestinal mucosal surface area to allow adequate absorption of nutrients to maintain body weight and support lifeThis entity has a multifactorial etiology and can occur in the pediatric population due to extensive intestinal resection resulting from gastroschisis, necrotizing enterocolitis, midgut volvulus, abdominal tumors and omphaloceles, as well as in diseases that are characterized by functional disturbances resulting from systemic aganglionosis (Hirshchsprung's disease) and inclusion of intestinal microvilli.In adults, extensive intestinal resections are due to Inflammatory Bowel Disease (Crohn's disease), complex abdominal trauma, thromboembolic events and vascular tumors with extensive involvement of the pedicle of the superior mesenteric artery are due to short bowel syndrome. The residual intestine should not be classified as short only by the extent of the remnant, but mainly by the absence of adaptation.Despite the support offered by prolonged parenteral nutrition and compensatory mechanisms that may occur in the remaining intestine, malabsorption originates long-term clinical control difficult situations, with high morbidity and mortality.At the same time, depending on the length of the remaining small intestine, several surgical techniques have been described to provide decreased intestinal transit time to increase the absorptive capacity of the gut or residual elongation. However, there are limitations to their effective use, with varying rates of success.After the development of numerous experimental studies directed to the treatment of short bowel syndrome, small bowel transplantation has emerged as an attractive alternative in these cases.The rejection of the transplanted graft is still the most common major complication, and infectious complications resulting from immunosuppression. Despite the advances of pharmacological agents, including antibiotics, antivirals and antifungals, keeps sepsis as the cause of death postoperatively, triggering periods of prolonged hospitalizations and expensive to funding institutions. Moreover, the cost of transplantation varies $ 200,000.00 to $ 400,000.00, and may reach values as $ 1,000,000.00 in the complications.Considering results below expectations with the numerous therapeutic modalities for the treatment of short bowel syndrome, the Tissue Engineering has been studied in order one day benefit patients with loss of gastrointestinal organs, providing a replacement tissue morphology and function similar to native tissue.In this sense, the present study aims to deploy techniques of tissue engineering, through enzymatic treatment for decellularization colon of rats and ex vivo repopulation with epithelial organoid units of autologous small intestine, aiming to produce new segments of small intestine in laboratory. (AU)