In vivo therapy for prenatal repair of the ovine fetal myelomeningocele model using human umbilical cord-derived mesenchymal stem cells: proof of principle

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Abstract Objectives Animal models suggest that combining mesenchymal stromal cells (MSCs) with prenatal myelomeningocele (MMC) repair may help preserve spinal cord function. This study assessed the feasibility of administration human umbilical cord-derived MSCs during prenatal repair of MMC in a sheep model. Methods MMC (L1–L5) were surgically created in 11 fetal lambs at 75 days. Seven underwent repair 25 days later – five with and two without MSCs. A high-dose, ready-to-use MSCs product (Desacell ® ), derived from healthy human neonatal umbilical cord tissue was administered in five cases. Each received 1 mL of Desacell ® gel containing 30 million MSCs directly to the spinal cord. All fetuses underwent multilayer dural myofascial patching and skin closure. Results Of the seven treated lambs, three (two with MSCs, one without) survived to term (144–147 days gestation). Motor function was evaluated using the sheep locomotor rating scale before euthanasia. MMC sites were excised en-bloc. Mean large neuron densities in gray matter were 20.4, 15, and 13.1 per mm 2 , respectively. Conclusions This is the first report of successful local administration of MSCs during in utero MMC repair in a sheep model using Desacell ® , a ready-to-use stem cell product. MSCs administration was feasible in all intended cases, however, the limited sample size restricted comparative outcomes analyses.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.