In utero repair of an experimental neural tube defect in a chronic sheep model using biomatrices

被引:41
作者
Eggink, AJ
Roelofs, LAJ
Feitz, WFJ
Wijnen, RMH
Mullaart, RA
Grotenhuis, JA
van Kuppevelt, TH
Lammens, MMY
Crevels, AJ
Hanssen, A
van den Berg, PP
机构
[1] Radboud Univ, Med Ctr, Dept Obstet & Gynecol, NL-6500 HB Nijmegen, Netherlands
[2] Radboud Univ, Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands
[3] Radboud Univ, Med Ctr, Dept Pediat Surg, NL-6500 HB Nijmegen, Netherlands
[4] Radboud Univ, Med Ctr, Dept Pediat Neurol, NL-6500 HB Nijmegen, Netherlands
[5] Radboud Univ, Med Ctr, Dept Neurosurg, NL-6500 HB Nijmegen, Netherlands
[6] Radboud Univ, Med Ctr, Dept Biochem, NL-6500 HB Nijmegen, Netherlands
[7] Radboud Univ, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands
[8] Radboud Univ, Med Ctr, Cent Anim Lab, NL-6500 HB Nijmegen, Netherlands
关键词
myelomeningocele; spina bifida; neural tube defect; fetal surgery; sheep; tissue engineering;
D O I
10.1159/000086808
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Objective: Persistent exposure of the unprotected spinal cord to amniotic fluid and the uterine wall can lead to progressive damage of neural tissue in case of a myelomeningocele (two-hit hypothesis). The aim of this study was to evaluate whether in utero repair of an experimental neural tube defect in a fetal lamb could protect neural tissue from secondary injury and save neurologic functions after birth. Methods: In 19fetal lambs, a neural tube defect was created at 79 days' gestation. In 12 lambs the defect was covered either with a novel, molecular defined collagen-based biocompatible and biodegradable matrix (UMC) or with a small intestinal submucosa (SIS) biomatrix (Cook (R)) or by closing the skin over the defect. Results: All lambs with the defect covered showed no or minor neurologic morbidity in contrast to the lambs with the defect uncovered in which major neurologic morbidity was seen. Conclusions: These results demonstrate that long-term exposure of the open spinal cord to the intrauterine environment can lead to damage of neural tissue and, consequently loss of neurologic functions and that coverage of the defect can lead to a better neurologic outcome. Furthermore, we could show that a UMC biomatrix and an SIS biomatrix are useful for in utero coverage of a surgically created neural tube defect in our model. Copyright (c) 2005 S. Karger AG, Basel.
引用
收藏
页码:335 / 340
页数:6
相关论文
共 21 条
[1]   In utero repair of myelomeningocele: A comparison of endoscopy and hysterotomy [J].
Bruner, JP ;
Tulipan, NB ;
Richards, WO ;
Walsh, WF ;
Boehm, FH ;
Vrabcak, EK .
FETAL DIAGNOSIS AND THERAPY, 2000, 15 (02) :83-88
[2]  
COPELAND ML, 1993, NEUROSURGERY, V33, P542
[3]   PREVENTION OF THE 1ST OCCURRENCE OF NEURAL-TUBE DEFECTS BY PERICONCEPTIONAL VITAMIN SUPPLEMENTATION [J].
CZEIZEL, AE ;
DUDAS, I .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 327 (26) :1832-1835
[4]   Feasibility of minimally invasive intrauterine fetal access in a monkey model [J].
Feitz, WFJ ;
Steegers, EAP ;
de Gier, RPE ;
Aarnink, RG ;
Arts, T ;
van der Wildt, B .
JOURNAL OF UROLOGY, 1999, 161 (01) :281-285
[5]   THE PARALYSIS ASSOCIATED WITH MYELOMENINGOCELE - CLINICAL AND EXPERIMENTAL-DATA IMPLICATING A PREVENTABLE SPINAL-CORD INJURY [J].
HEFFEZ, DS ;
ARYANPUR, J ;
HUTCHINS, GM ;
FREEMAN, JM .
NEUROSURGERY, 1990, 26 (06) :987-992
[6]   Fetal surgery for myelomeningocele: Panacea or peril? [J].
Hirose, S ;
Meuli-Simmen, C ;
Meuli, M .
WORLD JOURNAL OF SURGERY, 2003, 27 (01) :87-94
[7]  
Hutchins G. M., 1992, American Journal of Human Genetics, V51, pA319
[8]   CREATION OF MYELOMENINGOCELE IN-UTERO - A MODEL OF FUNCTIONAL DAMAGE FROM SPINAL-CORD EXPOSURE IN FETAL SHEEP [J].
MEULI, M ;
MEULISIMMEN, C ;
YINGLING, CD ;
HUTCHINS, GM ;
HOFFMAN, KM ;
HARRISON, MR ;
ADZICK, NS .
JOURNAL OF PEDIATRIC SURGERY, 1995, 30 (07) :1028-1033
[9]   IN-UTERO SURGERY RESCUES NEUROLOGICAL FUNCTION AT BIRTH IN SHEEP WITH SPINA-BIFIDA [J].
MEULI, M ;
MEULISIMMEN, C ;
HUTCHINS, GM ;
YINGLING, CD ;
HOFFMAN, KM ;
HARRISON, MR ;
ADZICK, NS .
NATURE MEDICINE, 1995, 1 (04) :342-347
[10]   In utero repair of experimental myelomeningocele saves neurological function at birth [J].
Meuli, M ;
MeuliSimmen, C ;
Yingling, CD ;
Hutchins, GM ;
Timmel, GB ;
Harrison, MR ;
Adzick, NS .
JOURNAL OF PEDIATRIC SURGERY, 1996, 31 (03) :397-402