Tissue-engineered neomucosa: morphology, enterocyte dynamics, and SGLT1 expression topography.
BACKGROUND
The standard therapy for short bowel syndrome is total parenteral nutrition, which is expensive and associated with significant morbidity and mortality. New therapeutic approaches for this disorder are needed. We have applied the techniques of tissue engineering to develop a prototype neointestine. We hypothesized that anastomosis of this neointestine to the native bowel would result in regeneration of mucosal morphology and enterocyte dynamics.


METHODS
Biodegradable polymers seeded with neonatal rat intestinal organoid units were implanted into the omenta of adult rats to form neointestinal cysts. Five weeks after implantation, side-to-side cyst-jejunal anastomoses were fashioned in one cohort of rats. Tissues were harvested from all rats at 5 months after implantation. Native jejunal (J) and non-anastomosed (N-N) and anastomosed (A-N) neointestinal tissues were assessed for morphology, epithelial cell proliferation (5-bromo-2-deoxyuridine immunohistochemistry), apoptotic rates (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay), and SGLT1 in situ hybridization.


RESULTS
Mucosal morphology, rates and topography of enterocyte proliferation, and transporter expression in A-N neointestine recapitulated those of native jejunum. Each of these features was rudimentary in N-N neointestine.


CONCLUSIONS
These results suggest that the tissue-engineered neomucosa can develop structural and dynamic features of the normal jejunum. Anastomosis to the native intestine is an essential step for neomucosal development. Tissue engineering offers promise as a novel approach to the treatment of patients suffering from short bowel syndrome.
Tavakkolizadeh
Ali
A
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Berger
Urs V
UV
Stephen
Antonia E
AE
Kim
Byung S
BS
Mooney
David
D
Hediger
Matthias A
MA
Ashley
Stanley W
SW
Vacanti
Joseph P
JP
Whang
Edward E
EE
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D020895:Enterocytes / Q000166:cytology*; D005260:Female; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000166:cytology*; D007583:Jejunum / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D051269:Sodium-Glucose Transporter 1; D023822:Tissue Engineering
D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1