News Release

Study on use of umbilical cord vs. biocellulose film for antenatal spina bifida repair

Regenerative patch may improve neurological outcomes

Peer-Reviewed Publication

Society for Maternal-Fetal Medicine

ATLANTA (Feb. 1, 2016)--In a study to be presented on Feb. 5 in an oral plenary session at 8 a.m. EST, at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting™, in Atlanta, researchers will present findings from a study titled, Cryopreserved Human Umbilical Cord (HUC) vs. Biocellulose Film (BCF) for Antenatal Spina Bifida Repair.

Spina Bifida is a birth defect where there is incomplete closing of the backbone and the coverings around the spinal cord. The birth defect is associated with lifelong disability and death due to complications. In-utero surgery has been recently shown to improve the ability to walk and to reduce the need for shunting of hydrocephalus. However, over half of these children do not benefit from the in-utero repair. Researchers are trying to find a regenerative patch material for repair that would further reduce morbidity after repair through decreased damage to the spinal cord from inflammation and scar formation. This study sought to compare two patches that can be used in utero to repair the closing of the backbone with material that will promote regeneration of different coverings of spine.

Although the study took place in a rat model of spina bifida, it provided promising results. The human umbilical cord patch was determined to promote cellular migration of epidermal, neuronal and endothelial cells with minimal inflammatory response compared to biocellulose film.

"By finding a patch that will regenerate coverings of the spinal cord, with minimal inflammation and scar formation, we hope to improve the outcomes of in-utero spina bifida repair. We have established more evidence in large animal models and human cases, which showed similar results. This is a initial step toward a safe minimally invasive in-utero repair." stated Ramesha Papanna, M.D., M.P.H., the principal investigator of the project at The Fetal Center, Children's Memorial Hermann Hospital Dept. OB/GYN McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth). Saul Snowise, M.D. is a fetal intervention fellow at The Fetal Center and has actively worked and participated under the guidance of his mentor Dr. Papanna in the development of this project. Dr. Snowise is the primary author of the study and will present the findings.

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A copy of the abstract is available at http://www.smfmnewsroom.org and below. For interviews please contact Vicki Bendure at Vicki@bendurepr.com 202-374-9259 (cell).

The Society for Maternal-Fetal Medicine (est. 1977) is the premiere membership organization for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine. The society is devoted to reducing high-risk pregnancy complications by sharing expertise through continuing education to its 2,000 members on the latest pregnancy assessment and treatment methods. It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine. The group hosts an annual meeting in which groundbreaking new ideas and research in the area of maternal-fetal medicine are shared and discussed. For more information visit http://www.smfm.org.

Abstract 47: Cryopreserved Human Umbilical Cord (HUC) vs. Biocellulose Film (BCF) for Antenatal Spina Bifida Repair
Authors: Saul Snowise1, Lovepreet Mann1, Mi-Ae Lyu1, Yisel Morales1, Kenneth J. Moise Jr.1, Stephen Fletcher1, Ray Grill2, Schaeffer CG Tseng3, Anthony Johnson1, Ramesha Papanna1
1The Fetal Center, Children's Memorial Hermann Hospital Dept. OB/GYN UT Health- University of Texas Medical School at Houston, Houston, TX, 2Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, 3Ocular Surface Center, Miami, FL

Objective: Antenatal fetoscopic spina bifida (SB) repair with a regenerative patch may improve neurological outcomes by allowing earlier intervention and decreasing inflammatory scarring. Our objective was to compare two patches, HUC and BCF sutured over SB lesions in a retinoic acid (RA) rat model, for regenerative ingrowth of native cells and associated inflammatory response.

Study Design: Pregnant time-dated Sprague-Dawley rats were gavaged with RA (40mg/kg) on gestational day 10 (GD10) to induce SB in pups. Laparotomy and hysterotomy were performed on GD20 and HUC (n=11) or BCF (n=10) sutured over the spinal defect. Patches placed into the amniotic cavity without suturing over the lesion were controls. 30-34 hours after grafting pups were harvested and formalin fixed. H&E and Trichrome staining assessed cellular migration into the patches. Immunohistochemistry was performed to demonstrate the nature of the cellular migration. Native cell markers evaluated were CK 5/6 (epidermal), GFAP (astrocytes) and vWF (endothelial). Inflammatory markers were CD3 (lymphocytes), MPO (neutrophils), and F4-80 (macrophages). Four high power fields (hpf) of all patches and surrounding exudates were evaluated and Image-J software was used to quantify cells.

Results: Pup survival was equal: HUC 8/11, BCF 7/10, (p=0.9). Histology showed cellular migration in all HUC patches applied over lesions (median:38[range;13-102] cells/hpf) compared to none in BCF patches (Figure; p<0.001). CK 5/6 positive cells were noted migrating over the HUC patch surface (4-7cells/hpf): GFAP positive cells were noted on the HUC patch surface adjacent to the lesion (3-11 cells/hpf); vWF positive cells were noted in the HUC patch (5-15cells/hpf). No CK 5/6, GFAP or vWF positive cells were noted in BCF patches (p=0.03). HUC patches showed minimal MPO (2%[0-7%]), CD3 (7%[3-12%]) and F4-80 (0%) positive cells. Exudates in HUC treated pups had fewer MPO (0%[0-9%] vs 17%[0-39%]; p<0.01) and CD3 (7%[0-13%] vs 15%[0-22%]; p<0.01) positive cells compared to BCF and demonstrated no difference in F4-80. Both HUC and BCF control patches demonstrated no infiltrate.

Conclusion: HUC promotes cellular migration of epidermal, neuronal and endothelial cells with minimal inflammatory response compared to BCF. HUC may be the ideal patch material for use in antenatal SB repair.


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