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ABSTRACT: Our laboratory is investigating the tissue engineering of small intestine using intestinal epithelial organoid units seeded onto highly porous biodegradable polymer matrices. This study investigated the effects of anastomosis of tissue-engineered intestine to native small bowel alone or combined with small bowel resection on neointestinal regeneration.
Intestinal epithelial organoid units harvested from neonatal Lewis rats were seeded onto biodegradable polymer tubes and implanted into the omentum of adult Lewis rats as follows: (1) implantation alone (n = 9); (2) implantation followed by anastomosis to native small bowel at 3 weeks (n = 11); and (3) implantation after small bowel resection and anastomosis to native small bowel at 3 weeks (n = 8). All constructs were harvested at 10 weeks and examined by histology. Morphometric analysis of the neomucosa was obtained using a computer image analysis program.
Cyst development was noted in all animals. All anastomoses were patent at 10 weeks. Histology revealed the development of a vascularized tissue with a neomucosa lining the lumen of the cyst with invaginations resembling crypt-villus structures. Morphometric analysis demonstrated significantly greater villus number, villus height, crypt number, crypt area, and mucosal surface length in groups 2 and 3 compared with group 1, and significantly greater villus number, villus height, crypt area, and mucosal surface length in group 3 compared with group 2 (P < 0.05, ANOVA, Tukey test).
Intestinal epithelial organoid units transplanted on biodegradable polymer tubes can regenerate into complex tissue resembling small intestine. Anastomosis to native small bowel combined with small bowel resection and anastomosis alone contribute significant regenerative stimuli for the morphogenesis and differentiation of tissue-engineered neointestine.
Journal of Surgical Research 12/1999; 87(1):6-13. · 2.25 Impact Factor
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ABSTRACT: Our laboratory is investigating the tissue engineering of small intestine using intestinal epithelial organoid units seeded onto highly porous biodegradable polymer tubes. This study investigated methods of stimulation for optimizing neointestinal regeneration.
Intestinal epithelial organoid units harvested from neonatal Lewis rats were seeded onto porous biodegradable polymer tubes and implanted into the omentum of adult Lewis rats in the following groups: (1) the control group (group C), implantation alone (n=9); (2) the small bowel resection (SBr) group, after 75% SBr (n=9); (3) the portacaval shunt (PCS) group, after PCS (n=8); and (4) the partial hepatectomy (PH) group, after 75% PH (n=8). Neointestinal cyst size was recorded using ultrasonography. Constructs were harvested at 10 weeks and were examined using histology. Morphometric analysis of the neomucosa was obtained using a computer image analysis program (NIH Image, version 1.59).
Cyst development was noted in all animals. Cyst lengths and diameters were significantly larger in the SBr group at 7 and 10 weeks compared with the other three groups (P<0.05; analysis of variance [ANOVA], Fisher's protected least significant difference). Histology revealed a well-vascularized tissue with a neomucosa lining the lumen with invaginations resembling crypt-villus structures. Morphometric analysis demonstrated a significantly greater villus number, height, area, and mucosal surface in the SBr group compared with the other three groups and a significantly greater crypt number and area in the PCS group compared with group C (P<0.05; ANOVA, Fisher's protected least significant difference).
Intestinal epithelial organoid units transplanted on porous biodegradable polymer tubes can successfully vascularize, survive, and regenerate into complex tissue resembling small intestine. SBr and, to a lesser extent, PCS provide significant regenerative stimuli for the morphogenesis and differentiation of tissue-engineered small intestine.
Transplantation 02/1999; 67(2):227-33. · 4.00 Impact Factor
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ABSTRACT: Previous studies have shown that intestinal crypt cell transplantation using biodegradable scaffolds can generate stratified epithelium reminiscent of embryonic gut. The authors propose to tissue engineer small intestine on biodegradable scaffolds by transplanting intestinal epithelial organoid units, which maintain the epithelial mesenchymal cell-cell interaction necessary for epithelial survival, proliferation, and differentiation.
Intestinal epithelial organoid units were isolated from neonatal Lewis rats by enzyme digestion and differential sedimentation. Organoid units were seeded on to tubular scaffolds made of nonwoven polyglycolic acid (PGA) sprayed with 5% polylactic acid (PLA). Polymers either were coated (28 constructs) or noncoated (33 constructs) with collagen type I. A total of 61 organoid unit polymer constructs were implanted into 61 animals. Animals were killed and constructs harvested at 2, 6, 7, 8, 9, 10, 12, and 14 weeks.
Histological analysis showed formation of neomucosa characterized by columnar epithelium with goblet, and paneth cells were evident in 47 of the 61 constructs. The outer walls were composed of fibrovascular tissue, degradable polymer, extracellular matrix, and smooth muscle-like cells. Immunofluorescent microscopy showed apical staining of brush border enzymes, sucrase and lactase, and basolateral staining for laminin, indicating the establishment of cell polarity. Electrophysiology of Ussing-chambered neomucosa and adult ileal mucosa exhibited similar transepithelial resistance.
These results suggest that intestinal crypt cells heterotopically transplanted as epithelial organoid units on PGA-PLA tubular scaffolds can survive, reorganize, and regenerate complex composite tissue resembling small intestine demonstrating organ morphogenesis, cytodifferentiation, and phenotypic maturation.
Journal of Pediatric Surgery 08/1998; 33(7):991-6; discussion 996-7. · 1.45 Impact Factor
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ABSTRACT: Caustic injury to the upper aerodigestive system with scarring of the pharynx, hypopharynx, and esophagus is a challenging reconstructive problem. The authors report on seven patients who required total esophageal replacement from the pharynx to the stomach. Injury occurred from alkali in six and acid in one. Age at injury ranged from 14 months to 14 years (mean, 4.5 years.) in five boys and two girls. Time from injury to esophageal replacement was 6 months to 10 years (mean, 3.5 years). Two required pharyngeal reconstruction before and one after esophageal replacement. Six patients had an isoperistaltic right or transverse colon interposition. One who had gastric necrosis had an ileo-right colonic substernal interposition with creation of a jejunal reservoir. Results of barium swallows showed intact anastomoses in all patients. There were no leaks. Most had some degree of mild to moderate aspiration, and one who had left vocal cord paralysis had initially massive aspiration. Three patients currently eat regular diets; four eat but still require supplemental tube feeds. The authors conclude that children who have hypopharyngeal scarring and obliterated esophageal inlet can undergo a successful colonic esophageal replacement with high proximal pharyngocolic anastomosis.
Journal of Pediatric Surgery 08/1997; 32(7):1083-7; discussion 1087-8. · 1.45 Impact Factor
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Transplantation Proceedings 29(1-2):848-51. · 1.00 Impact Factor
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Transplantation Proceedings 31(1-2):657-60. · 1.00 Impact Factor
