Tissue-engineered Small Intestine Improves Recovery After Massive Small Bowel Resection

Overview

Journal Ann Surg

Specialty General Surgery

Date 2004 Oct 20

PMID 15492554

Citations 76

Authors

Tracy C Grikscheit

Aleem Siddique

Erin R Ochoa

Ashok Srinivasan

Eben Alsberg

Richard A Hodin

Joseph P Vacanti

Affiliations

Soon will be listed here.

Abstract

Objective: Rescue with tissue-engineered small intestine (TESI) after massive small bowel resection (MSBR).

Summary Background Data: Short bowel syndrome is a morbid product of massive small bowel resection. We report the first replacement of a vital organ by tissue engineering with TESI after MSBR.

Methods: Ten male Lewis rats underwent TESI implantation with green fluorescent protein (GFP)-marked cells (TESI+, n = 5) or sham laparotomy (TESI-, n = 5) followed by MSBR. Side-to-side anastomosis of TESI to proximal small intestine was performed or omitted. TESIO animals underwent implantation of engineered intestine with no further surgery. Weights were measured QOD until day 40. Transit times were measured. DNA assay was performed with computer morphometry. Northern blots of RNA were probed for intestinal alkaline phosphatase (IAP) and villin. Hematoxylin and eosin, S100, and smooth muscle actin immunohistochemistry were performed. Blood was collected at sacrifice.

Results: All 10 rats initially lost then regained weight. The initial rate of weight loss was higher in TESI+ versus TESI-, but the nadir was reached a week earlier with more rapid weight gain subsequently to 98% preoperative weight on day 40 in animals with engineered intestine versus 76% (P < 0.03). Serum B12 was higher at 439 pg/mL versus 195.4 pg/mL. IAP mRNA appeared greater in TESI+ than TESIO, with constant villin levels. Histology revealed appropriate architecture including nerve. GFP labeling persisted.

Conclusions: Anastomosis of TESI significantly improved postoperative weight and B12 absorption after MSBR. IAP, a marker of differentiation in intestinal epithelium, is present in TESI, and GFP labeling was accomplished.

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References

Choi R, Vacanti J . Preliminary studies of tissue-engineered intestine using isolated epithelial organoid units on tubular synthetic biodegradable scaffolds. Transplant Proc. 1997; 29(1-2):848-51. DOI: 10.1016/s0041-1345(96)00164-9. View

Nightingale J, Kamm M, van der Sijp J, Ghatei M, Bloom S, Lennard-Jones J . Gastrointestinal hormones in short bowel syndrome. Peptide YY may be the 'colonic brake' to gastric emptying. Gut. 1996; 39(2):267-72. PMC: 1383310. DOI: 10.1136/gut.39.2.267. View

Lykins T, Stockwell J . Comprehensive modified diet simplifies nutrition management of adults with short-bowel syndrome. J Am Diet Assoc. 1998; 98(3):309-15. DOI: 10.1016/S0002-8223(98)00072-8. View

Choi R, Riegler M, Pothoulakis C, Kim B, Mooney D, Vacanti M . Studies of brush border enzymes, basement membrane components, and electrophysiology of tissue-engineered neointestine. J Pediatr Surg. 1998; 33(7):991-6; discussion 996-7. DOI: 10.1016/s0022-3468(98)90520-6. View

Moog F . Developmental adaptations of alkaline phosphatases in the small intestine. Fed Proc. 1962; 21:51-6. View

Sundaram A, Koutkia P, Apovian C . Nutritional management of short bowel syndrome in adults. J Clin Gastroenterol. 2002; 34(3):207-20. DOI: 10.1097/00004836-200203000-00003. View

Grikscheit T, Ogilvie J, Ochoa E, Alsberg E, Mooney D, Vacanti J . Tissue-engineered colon exhibits function in vivo. Surgery. 2002; 132(2):200-4. DOI: 10.1067/msy.2002.125310. View

Perez A, Grikscheit T, Blumberg R, Ashley S, Vacanti J, Whang E . Tissue-engineered small intestine: ontogeny of the immune system. Transplantation. 2002; 74(5):619-23. DOI: 10.1097/00007890-200209150-00006. View

Grikscheit T, Ochoa E, Ramsanahie A, Alsberg E, Mooney D, Whang E . Tissue-engineered large intestine resembles native colon with appropriate in vitro physiology and architecture. Ann Surg. 2003; 238(1):35-41. PMC: 1422658. DOI: 10.1097/01.SLA.0000074964.77367.4a. View

10.

Grikscheit T, Ochoa E, Srinivasan A, Gaissert H, Vacanti J . Tissue-engineered esophagus: experimental substitution by onlay patch or interposition. J Thorac Cardiovasc Surg. 2003; 126(2):537-44. DOI: 10.1016/s0022-5223(03)00032-1. View

11.

Grikscheit T, Srinivasan A, Vacanti J . Tissue-engineered stomach: a preliminary report of a versatile in vivo model with therapeutic potential. J Pediatr Surg. 2003; 38(9):1305-9. DOI: 10.1016/s0022-3468(03)00386-5. View

12.

Ramsanahie A, Duxbury M, Grikscheit T, Perez A, Rhoads D, Gardner-Thorpe J . Effect of GLP-2 on mucosal morphology and SGLT1 expression in tissue-engineered neointestine. Am J Physiol Gastrointest Liver Physiol. 2003; 285(6):G1345-52. DOI: 10.1152/ajpgi.00374.2002. View

13.

Cleveland D, Lopata M, MacDonald R, Cowan N, Rutter W, Kirschner M . Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980; 20(1):95-105. DOI: 10.1016/0092-8674(80)90238-x. View

14.

Henthorn P, Raducha M, Edwards Y, Weiss M, Slaughter C, Lafferty M . Nucleotide and amino acid sequences of human intestinal alkaline phosphatase: close homology to placental alkaline phosphatase. Proc Natl Acad Sci U S A. 1987; 84(5):1234-8. PMC: 304401. DOI: 10.1073/pnas.84.5.1234. View

15.

Arpin M, Pringault E, Finidori J, Garcia A, Jeltsch J, Vandekerckhove J . Sequence of human villin: a large duplicated domain homologous with other actin-severing proteins and a unique small carboxy-terminal domain related to villin specificity. J Cell Biol. 1988; 107(5):1759-66. PMC: 2115311. DOI: 10.1083/jcb.107.5.1759. View

16.

Evans G, Flint N, Somers A, Eyden B, Potten C . The development of a method for the preparation of rat intestinal epithelial cell primary cultures. J Cell Sci. 1992; 101 ( Pt 1):219-31. DOI: 10.1242/jcs.101.1.219. View

17.

Robine S, Louvard D, Pringault E . Regulatory sequences on the human villin gene trigger the expression of a reporter gene in a differentiating HT29 intestinal cell line. J Biol Chem. 1993; 268(15):11426-34. View

18.

Thompson J . Management of the short bowel syndrome. Gastroenterol Clin North Am. 1994; 23(2):403-20. View

19.

Stollman N, Neustater B, Rogers A . Short-bowel syndrome. Gastroenterologist. 1996; 4(2):118-28. View

20.

Ory D, Neugeboren B, Mulligan R . A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes. Proc Natl Acad Sci U S A. 1996; 93(21):11400-6. PMC: 38069. DOI: 10.1073/pnas.93.21.11400. View