Tissue-engineered small intestine improves recovery after massive small bowel resection.
OBJECTIVE
Rescue with tissue-engineered small intestine (TESI) after massive small bowel resection (MSBR).


BACKGROUND
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.
Grikscheit
Tracy C
TC
Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Siddique
Aleem
A
Ochoa
Erin R
ER
Srinivasan
Ashok
A
Alsberg
Eben
E
Hodin
Richard A
RA
Vacanti
Joseph P
JP
D000199:Actins / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D005755:Gastrins / Q000097:blood; D005772:Gastrointestinal Transit; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism / Q000601:surgery / Q000637:transplantation*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009940:Organoids / Q000637:transplantation; D012313:RNA / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D009418:S100 Proteins / Q000378:metabolism; D023822:Tissue Engineering; D014805:Vitamin B 12 / Q000097:blood
D000199:Actins; D005755:Gastrins; D008840:Microfilament Proteins; D009418:S100 Proteins; C026615:villin; D012313:RNA; D000469:Alkaline Phosphatase; D014805:Vitamin B 12