Tissue Engineering Strategies for Fetal MMC Repair

While the MOMS trial has demonstrated conclusively that open fetal surgery for repair of myelomeningocele (MMC) improves outcomes — with reduction in hindbrain herniation and the need for shunting, and significant improvement in functional neurologic outcomes — open fetal surgery for MMC is not a cure. Most patients demonstrate some degree of residual neurologic deficit, and some fetuses demonstrate no benefit over predicted neurologic function.

The Center for Fetal Research, the research extension of CHOP’s Center for Fetal Diagnosis and Treatment, continues to seek to improve prenatal treatment of MMC through a less invasive approach that would allow for application earlier in gestation, with reduction in maternal and fetal risks, and the potential for reduced neurologic injury. Our research has found tissue engineering offers a realistic and appealing alternative approach for the prenatal treatment of MMC.

Our laboratory has been testing and optimizing a variety of scaffolds, cells and growth factors to develop a tissue engineering construct that will ultimately be clinically applicable for prenatal closure of MMC. A true paradigm-changing prenatal therapy for MMC would:

• Be applicable by ultrasound-guided injection or by single port fetoscopy at much earlier gestational time points, ideally by 15 to 18 weeks gestation
• Incorporate tissue engineering principles of an injectable scaffold of biocompatible material that would be secured over the MMC defect by either adhesive or sheet application or both
• Potentially contain growth factors to stimulate endogenous stem cell activity, and provide neurotrophic or protective activity
• Generate a fluid-impermeable tissue layer without adherence to the underlying neural placode

This is a challenging ideal, but it can conceivably be accomplished with current technology. Leveraging multidisciplinary collaborations between fetal therapists, tissue engineers, stem cell biologists and other experts, our team is working to develop creative solutions to the current challenges in prenatal surgical repair of MMC and to design clinical studies that compare the new technique to the established standard of open fetal surgical repair.

References

Watanabe M, Kim AG, Flake AW. Tissue Engineering Strategies for Fetal Myelomeningocele Repair in Animal Models. Fetal Diagn Ther. 2014 Jul 19. [Epub ahead of print]

Adzick NS. Fetal Surgery for Spina Bifida: Past, Present, Future. Semin Pediatr Surg. 2013 Feb; 22(1): 10–17.

Watanabe M, Li H, Roybal J, Santore M, Radu A, Jo J, Kaneko M, Tabata Y, Flake A. A Tissue Engineering Approach for Prenatal Closure of Myelomeningocele: Comparison of Gelatin Sponge and Microsphere Scaffolds and Bioactive Protein Coatings. Tissue Eng Part A. 2011 Apr;17(7-8):1099-110.