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Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model
Lovepreet K Mann1, Jong Hak Won1, Rajan Patel2
1Division of Maternal-Fetal Medicine, The Fetal Center at Children's Memorial Hermann Hospital, Department of Obstetrics, Gynecology and Reproductive Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA.
Human umbilical cord (HUC) patches significantly improve spinal cord function in spina bifida (SB) repairs compared to acellular dermal matrix (ADM). HUC reduces inflammation and preserves neurological outcomes in lambs, offering a promising regenerative approach for SB.
Area of Science:
- Regenerative Medicine
- Developmental Biology
- Neuroscience
Background:
- Off-label use of acellular dermal matrix (ADM) for in utero spina bifida (SB) repair is linked to poor neurological outcomes.
- Cryopreserved human umbilical cord (HUC) possesses regenerative, anti-inflammatory, and anti-scarring properties, enabling watertight SB repair.
Purpose of the Study:
- To evaluate the efficacy of HUC as a superior skin patch compared to ADM for reducing inflammation and preserving spinal cord function in a fetal SB repair model.
- To test the hypothesis that HUC outperforms ADM in mitigating inflammation and maintaining neurological function post-repair.
Main Methods:
- A functional spina bifida model was created in fetal lambs (gestational day 75).
- Repairs were performed on gestational day 95 using HUC or ADM patches, with primary skin closure (PSC) as a positive control.
- Neurological assessments (gait, proprioception, nociception) were conducted post-delivery (gestational day 140) using the Texas Spinal Cord Injury Scale (TSCIS).
- Ex vivo MRI and histological analyses (Masson's trichrome, immunofluorescence for MPO and astrocytes) were performed to assess pathological changes.
Main Results:
- The HUC group showed significantly higher combined hind limb TSCIS scores compared to ADM and PSC groups (p = 0.007).
- ADM and PSC groups exhibited impaired proprioception and ataxia, unlike controls and the HUC group.
- Histological analysis revealed reduced meningeal thickening and lower neutrophil (MPO) and astrocyte activation in the HUC group compared to ADM and PSC groups (p < 0.05).
Conclusions:
- Human umbilical cord (HUC) patches serve as a superior alternative to acellular dermal matrix (ADM) for in utero spina bifida repair.
- HUC application effectively preserves spinal cord function by significantly reducing inflammation at the repair site.
- These findings highlight the regenerative potential of HUC in improving outcomes for congenital conditions like spina bifida.
