154 Placental MSCs for in utero myelomeningocele repair do not present additional risk for pregnant ewes

Abstract

Fetal surgical repair of myelomeningocele (MMC) has become the established standard of care for eligible women. Despite the childhood advances associated with in utero repair, room for neurologic improvement remains. We have demonstrated that using early gestation human placental mesenchymal stromal cells seeded on to an extracellular dural matrix (PMSC-ECM) to augment the in utero repair of MMC results in significantly improved motor outcomes. In preparation for clinical trials, this study aimed to establish the safety of use of a PMSC-ECM patch in utero in an ovine model. Ewes underwent surgical intervention in which a hysterotomy was created, the fetal back was operated on and the spinal cord exposed. A PMSC-ECM patch was placed directly onto the spinal cord, the fetal paraspinal muscles and skin were closed, and the fetus was returned to the uterus. Fetuses were delivered via Cesarean section and placental tissue was collected. Ewes were monitored for three months post-partum and then euthanized. A complete blood count and comprehensive metabolic panel were collected at the time of euthanasia. Ewes were dissected and uteri collected. Uteri and placentas underwent histological evaluation for evidence of tumor formation and polymerase chain reaction to evaluate for persistent human DNA to indicate retention of PMSCs. Seven ewes underwent surgical intervention between 100-106 days gestation, fetuses were delivered between 140-142 days. No ewes developed complications during pregnancy or post-partum and no anomalies were noted at dissection. Bloodwork collected from the ewes was within normal limits. Placentas from 5 ewes and uteri from all 7 ewes were collected. There was no evidence of tumor formation or persistence of human PMSCs in the uteri or placentas. The in utero use of a PMSC-ECM patch in an ovine model does not result in maternal tumor formation or persistence of PMSCs. These results add support to the safety of proceeding with first in human clinical trial of a PMSC-ECM patch in human patients with MMC.