Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair

• Published in: Journal of pediatric surgery Vol. 57; no. 5; pp. 941 - 948
• Main Authors: Theodorou, Christina M., Jackson, Jordan E., Stokes, Sarah C., Pivetti, Christopher D., Kumar, Priyadarsini, Paxton, Zachary J., Matsukuma, Karen E., Yamashiro, Kaeli J., Reynaga, Lizette, Hyllen, Alicia A., de Lorimier, Arthur J., Hassan, Maheen, Wang, Aijun, Farmer, Diana L., Saadai, Payam
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2022
• Subjects: Animals; Bladder function; Bowel function; Cellular therapy; Female; Fetal surgery; Fetus - surgery; Humans; Meningomyelocele - complications; Meningomyelocele - surgery; Mesenchymal Stem Cells; Myelomeningocele; Placenta; Pregnancy; Sheep; Sheep, Domestic; Spina bifida; Urinary Bladder - surgery; Bladder function; Fetal surgery; Spina bifida; Myelomeningocele; Bowel function; Cellular therapy
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/j.jpedsurg.2021.12.046

•Myelomeningocele is associated with significant bowel and bladder dysfunction.•Fetal ovine myelomeningocele repair augmented with placental mesenchymal stem cells was associated with near-normal bowel and bladder function.
Fetal myelomeningocele (MMC) repair improves lower extremity motor function. We have previously demonstrated that augmentation of fetal MMC repair with placental mesenchymal stromal cells (PMSCs) seeded on extracellular matrix (PMSC-ECM) further improves motor function in the ovine model. However, little progress has been made in improving bowel and bladder function, with many patients suffering from neurogenic bowel and bladder. We hypothesized that fetal MMC repair with PMSC-ECM would also improve bowel and bladder function.
MMC defects were surgically created in twelve ovine fetuses at median gestational age (GA) 73 days, followed by defect repair at GA101 with PMSC-ECM. Fetuses were delivered at GA141. Primary bladder function outcomes were voiding posture and void volumes. Primary bowel function outcome was anorectal manometry findings including resting anal pressure and presence of rectoanal inhibitory reflex (RAIR). Secondary outcomes were anorectal and bladder detrusor muscle thickness. PMSC-ECM lambs were compared to normal lambs (n = 3).
Eighty percent of PMSC-ECM lambs displayed normal voiding posture compared to 100% of normal lambs (p = 1). Void volumes were similar (PMSC-ECM 6.1 ml/kg vs. normal 8.8 ml/kg, p = 0.4). Resting mean anal pressures were similar between cohorts (27.0 mmHg PMSC-ECM vs. normal 23.5 mmHg, p = 0.57). RAIR was present in 3/5 PMSC-ECM lambs that underwent anorectal manometry and all normal lambs (p = 0.46). Thicknesses of anal sphincter complex, rectal wall muscles, and bladder detrusor muscles were similar between cohorts.
Ovine fetal MMC repair augmented with PMSC-ECM results in near-normal bowel and bladder function. Further work is needed to evaluate these outcomes in human patients.