AJP Rep 2016; 06(03): e309-e317
DOI: 10.1055/s-0036-1592316
Case Report
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neurological Outcomes after Human Umbilical Cord Patch for In Utero Spina Bifida Repair in a Sheep Model

Ramesha Papanna
1   Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Medicine, UTHealth, The University of Texas Health Science at Houston, McGovern Medical School and the Fetal Center at Children's Memorial Hermann Hospital, Houston, Texas
,
Lovepreet K. Mann
1   Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Medicine, UTHealth, The University of Texas Health Science at Houston, McGovern Medical School and the Fetal Center at Children's Memorial Hermann Hospital, Houston, Texas
,
Saul Snowise
1   Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Medicine, UTHealth, The University of Texas Health Science at Houston, McGovern Medical School and the Fetal Center at Children's Memorial Hermann Hospital, Houston, Texas
,
Yisel Morales
1   Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Medicine, UTHealth, The University of Texas Health Science at Houston, McGovern Medical School and the Fetal Center at Children's Memorial Hermann Hospital, Houston, Texas
,
Sanjay P. Prabhu
2   Department of Radiology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts
,
Scheffer C. G. Tseng
3   The Ocular Surface Center, Miami, Florida
4   TissueTech, Inc., Miami, Florida
,
Raymond Grill
5   Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi
,
Stephen Fletcher
6   Division of Pediatric Neurosurgery, The Department of Pediatrics, UTHealth, The University of Texas Health Science at Houston, McGovern Medical School, Houston, Texas
7   Department of Pediatric Surgery, UTHealth, The University of Texas Health Science at Houston, McGovern Medical School, Houston, Texas
,
Kenneth J. Moise Jr.
1   Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Medicine, UTHealth, The University of Texas Health Science at Houston, McGovern Medical School and the Fetal Center at Children's Memorial Hermann Hospital, Houston, Texas
› Author Affiliations
Further Information

Publication History

19 July 2016

27 July 2016

Publication Date:
09 September 2016 (online)

Abstract

Objectives The objective of our study was to test the hypothesis that in utero repair of surgically created spina bifida in a sheep model using cryopreserved human umbilical cord (HUC) patch improves neurological outcome.

Methods Spina bifida with myelotomy was surgically created in timed pregnant ewes at gestational day (GD) 75. The fetuses were randomly assigned to unrepaired versus HUC and treated at GD 95 and then delivered at GD 140. Neurological evaluation was performed using the Texas Spinal Cord Injury Scale (TSCIS), bladder control using ultrasound, and the hindbrain herniation.

Results Three lambs without the spina bifida creation served as controls. There were four lambs with spina bifida: two were unrepaired and two underwent HUC repair. The control lambs had normal function. Both unrepaired lambs had nonhealed skin lesions with leakage of cerebrospinal fluid, a 0/20 TSCIS score, no bladder control, and the hindbrain herniation. In contrast, both HUC lambs had a completely healed skin defect and survived to day 2 of life, a 3/20 and 4/20 TSCIS score (nociception), partial bladder control, and normal hindbrain anatomy.

Conclusions Cryopreserved HUC patch appears to improve survival and neurological outcome in this severe form of the ovine model of spina bifida.

Note

This study was presented as an oral presentation at the 36th Annual Meeting of the Society for Maternal Fetal Medicine; 1–6 February, 2016; Atlanta, GA. Abstract no. 52.


 
  • References

  • 1 Adzick NS, Thom EA, Spong CY , et al; MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 2011; 364 (11) 993-1004
  • 2 Williams H. A unifying hypothesis for hydrocephalus, Chiari malformation, syringomyelia, anencephaly and spina bifida. Cerebrospinal Fluid Res 2008; 5: 7
  • 3 Mehta VA, Bettegowda C, Ahmadi SA , et al. Spinal cord tethering following myelomeningocele repair. J Neurosurg Pediatr 2010; 6 (5) 498-505
  • 4 Stavrinou P, Kunz M, Lehner M , et al. Children with tethered cord syndrome of different etiology benefit from microsurgery-a single institution experience. Childs Nerv Syst 2011; 27 (5) 803-810
  • 5 Levi B, Sugg KB, Lien SC , et al. Outcomes of tethered cord repair with a layered soft tissue closure. Ann Plast Surg 2013; 70 (1) 74-78
  • 6 Watanabe M, Kim AG, Flake AW. Tissue engineering strategies for fetal myelomeningocele repair in animal models. Fetal Diagn Ther 2015; 37 (3) 197-205
  • 7 Papanna R, Moise Jr KJ, Mann LK , et al. Cryopreserved human umbilical cord patch for in-utero spina bifida repair. Ultrasound Obstet Gynecol 2016; 47 (2) 168-176
  • 8 Liu J, Sheha H, Fu Y, Liang L, Tseng SC. Update on amniotic membrane transplantation. Expert Rev Ophthalmol 2010; 5 (5) 645-661
  • 9 Acharya G, Pavlovic M, Ewing L, Nollmann D, Leshko J, Huhta JC. Comparison between pulsed-wave Doppler- and tissue Doppler-derived Tei indices in fetuses with and without congenital heart disease. Ultrasound Obstet Gynecol 2008; 31 (4) 406-411
  • 10 Dua HS, Gomes JA, King AJ, Maharajan VS. The amniotic membrane in ophthalmology. Surv Ophthalmol 2004; 49 (1) 51-77
  • 11 Bouchard CS, John T. Amniotic membrane transplantation in the management of severe ocular surface disease: indications and outcomes. Ocul Surf 2004; 2 (3) 201-211
  • 12 Cooke M, Tan EK, Mandrycky C, He H, O'Connell J, Tseng SC. Comparison of cryopreserved amniotic membrane and umbilical cord tissue with dehydrated amniotic membrane/chorion tissue. J Wound Care 2014; 23 (10) 465-474 , 476
  • 13 Meuli M, Meuli-Simmen C, Hutchins GM , et al. In utero surgery rescues neurological function at birth in sheep with spina bifida. Nat Med 1995; 1 (4) 342-347
  • 14 Brown EG, Saadai P, Pivetti CD , et al. In utero repair of myelomeningocele with autologous amniotic membrane in the fetal lamb model. J Pediatr Surg 2014; 49 (1) 133-137 , discussion 137–138
  • 15 Levine GJ, Levine JM, Budke CM , et al. Description and repeatability of a newly developed spinal cord injury scale for dogs. Prev Vet Med 2009; 89 (1–2) 121-127
  • 16 Olby NJ, De Risio L, Muñana KR , et al. Development of a functional scoring system in dogs with acute spinal cord injuries. Am J Vet Res 2001; 62 (10) 1624-1628
  • 17 Stokes BT, Noyes DH, Behrmann DL. An electromechanical spinal injury technique with dynamic sensitivity. J Neurotrauma 1992; 9 (3) 187-195
  • 18 Levine JM, Levine GJ, Kerwin SC, Hettlich BF, Fosgate GT. Association between various physical factors and acute thoracolumbar intervertebral disk extrusion or protrusion in Dachshunds. J Am Vet Med Assoc 2006; 229 (3) 370-375
  • 19 Horváth G, Morvay Z, Kovács M, Szikszay M, Benedek G. An ultrasonographic method for the evaluation of dexmedetomidine on micturition in intact rats. J Pharmacol Toxicol Methods 1994; 32 (4) 215-218
  • 20 Hennig J, Nauerth A, Friedburg H. RARE imaging: a fast imaging method for clinical MR. Magn Reson Med 1986; 3 (6) 823-833
  • 21 Bouchard S, Davey MG, Rintoul NE, Walsh DS, Rorke LB, Adzick NS. Correction of hindbrain herniation and anatomy of the vermis after in utero repair of myelomeningocele in sheep. J Pediatr Surg 2003; 38 (3) 451-458 , discussion 451–458
  • 22 Tulipan N, Wellons III JC, Thom EA , et al; MOMS Investigators. Prenatal surgery for myelomeningocele and the need for cerebrospinal fluid shunt placement. J Neurosurg Pediatr 2015; 16 (6) 613-620
  • 23 Paek BW, Farmer DL, Wilkinson CC , et al. Hindbrain herniation develops in surgically created myelomeningocele but is absent after repair in fetal lambs. Am J Obstet Gynecol 2000; 183 (5) 1119-1123
  • 24 McMahill BG, Borjesson DL, Sieber-Blum M, Nolta JA, Sturges BK. Stem cells in canine spinal cord injury—promise for regenerative therapy in a large animal model of human disease. Stem Cell Rev 2015; 11 (1) 180-193
  • 25 Brown EG, Keller BA, Pivetti CD , et al. Development of a locomotor rating scale for testing motor function in sheep. J Pediatr Surg 2015; 50 (4) 617-621
  • 26 Meuli-Simmen C, Meuli M, Hutchins GM , et al. The fetal spinal cord does not regenerate after in utero transection in a large mammalian model. Neurosurgery 1996; 39 (3) 555-560 , discussion 560–561
  • 27 Chmait RH, Korst LM, Llanes A, Mullin P, Lee RH, Ouzounian JG. Perioperative characteristics associated with preterm birth in twin-twin transfusion syndrome treated by laser surgery. Am J Obstet Gynecol 2013; 209 (3) 264.e1-264.e8
  • 28 Wasner G, Lee BB, Engel S, McLachlan E. Residual spinothalamic tract pathways predict development of central pain after spinal cord injury. Brain 2008; 131 (Pt 9): 2387-2400
  • 29 Xiao CG, Du MX, Li B , et al. An artificial somatic-autonomic reflex pathway procedure for bladder control in children with spina bifida. J Urol 2005; 173 (6) 2112-2116
  • 30 Panicker JN, Fowler CJ, Kessler TM. Lower urinary tract dysfunction in the neurological patient: clinical assessment and management. Lancet Neurol 2015; 14 (7) 720-732
  • 31 Kessler TM, Lackner J, Kiss G, Rehder P, Madersbacher H. Predictive value of initial urodynamic pattern on urinary continence in patients with myelomeningocele. Neurourol Urodyn 2006; 25 (4) 361-367
  • 32 Cahill RA, Kiely EA. The spectrum of urological disease in patients with spina bifida. Ir J Med Sci 2003; 172 (4) 180-184
  • 33 Snow-Lisy DC, Yerkes EB, Cheng EY. Update on Urological Management of Spina Bifida from Prenatal Diagnosis to Adulthood. J Urol 2015; 194 (2) 288-296
  • 34 Andersson KE, Arner A. Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev 2004; 84 (3) 935-986
  • 35 He H, Li W, Tseng DY , et al. Biochemical characterization and function of complexes formed by hyaluronan and the heavy chains of inter-alpha-inhibitor (HC*HA) purified from extracts of human amniotic membrane. J Biol Chem 2009; 284 (30) 20136-20146
  • 36 Zhang S, He H, Day AJ, Tseng SC. Constitutive expression of inter-α-inhibitor (IαI) family proteins and tumor necrosis factor-stimulated gene-6 (TSG-6) by human amniotic membrane epithelial and stromal cells supporting formation of the heavy chain-hyaluronan (HC-HA) complex. J Biol Chem 2012; 287 (15) 12433-12444
  • 37 He H, Zhang S, Tighe S, Son J, Tseng SC. Immobilized heavy chain-hyaluronic acid polarizes lipopolysaccharide-activated macrophages toward M2 phenotype. J Biol Chem 2013; 288 (36) 25792-25803
  • 38 He H, Tan Y, Duffort S, Perez VL, Tseng SC. In vivo downregulation of innate and adaptive immune responses in corneal allograft rejection by HC-HA/PTX3 complex purified from amniotic membrane. Invest Ophthalmol Vis Sci 2014; 55 (3) 1647-1656
  • 39 Zhang S, Zhu YT, Chen SY, He H, Tseng SC. Constitutive expression of pentraxin 3 (PTX3) protein by human amniotic membrane cells leads to formation of the heavy chain (HC)-hyaluronan (HA)-PTX3 complex. J Biol Chem 2014; 289 (19) 13531-13542
  • 40 Tseng SC, Espana EM, Kawakita T , et al. How does amniotic membrane work?. Ocul Surf 2004; 2 (3) 177-187
  • 41 Chen SY, Han B, Zhu YT , et al. HC-HA/PTX3 Purified From Amniotic Membrane Promotes BMP Signaling in Limbal Niche Cells to Maintain Quiescence of Limbal Epithelial Progenitor/Stem Cells. Stem Cells 2015; 33 (11) 3341-3355
  • 42 Wang A, Brown EG, Lankford L , et al. Placental mesenchymal stromal cells rescue ambulation in ovine myelomeningocele. Stem Cells Transl Med 2015; 4 (6) 659-669