Tissue-engineered small intestine improves recovery after massive small bowel resection

Tissue-engineered small intestine improves recovery after massive small bowel resection
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DOI:
10.1097/01.sla.0000143246.07277.73
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发表时间:
2004-11-01
期刊:
影响因子:
9
通讯作者:
Vacanti, JP
Vacanti, JP
中科院分区:
医学1区
文献类型:
--
作者:
Grikscheit, TC;Siddique, A;Vacanti, JP

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目的:大面积小肠切除术(MSBR)后用组织工程小肠(TEST)进行抢救。背景资料:短肠综合征是大面积小肠切除术的病态产物。方法:10只雄性刘易斯大鼠行绿色荧光蛋白(GFP)标记的细胞(TESI+,n = 5)或假剖腹术(TESI,n = 5)后行MSBR。进行或省略了供试品与近端小肠的侧侧吻合。TESIcircle divide动物接受了工程化肠的植入,没有进一步的手术。QOD测量体重直至第40天。测量通过时间。DNA含量测定采用计算机形态计量学。对RNA的北方印迹进行肠碱性磷酸酶(TAP)和绒毛蛋白的探测。进行苏木精-伊红、5100和平滑肌肌动蛋白免疫组化。结果:所有10只大鼠最初体重下降,然后恢复。TESI+组的初始体重减轻率高于TESI-组,但在一周前达到最低点,随后体重增加更快,在第40天,工程化肠道动物的术前体重达到98%,而工程化肠道动物的术前体重增加率为76%(P < 0.03)。血清B12高于439 pg/mL和195.4 pg/mL。IAP mRNA在TESI+中比TESIcircle divide更高,绒毛蛋白水平恒定。组织学显示适当的结构,包括神经。结论:TEST吻合术显著改善了MSBR术后体重和B12吸收。TAP是肠上皮分化的标志物,存在于TEST中,并完成GFP标记。
Objective: Rescue with tissue-engineered small intestine (TEST) 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 TEST to proximal small intestine was performed or omitted. TESIcircle divide 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 (TAP) and villin. Hematoxylin and eosin, 5100, 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 TESIcircle divide, with constant villin levels. Histology revealed appropriate architecture including nerve. GFP labeling persisted.Conclusions: Anastomosis of TEST significantly improved postoperative weight and B12 absorption after MSBR. TAP, a marker of differentiation in intestinal epithelium, is present in TEST, and GFP labeling was accomplished.