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

Introduction: 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.

Long-term safety evaluation of placental mesenchymal stromal cells for in utero repair of myelomeningocele in a novel ovine model.

Purpose: Augmentation of in utero myelomeningocele repair with human placental mesenchymal stromal cells seeded onto extracellular matrix (PMSC-ECM) improves motor outcomes in an ovine myelomeningocele model. This study evaluated the safety of PMSC-ECM application directly onto the fetal spinal cord in preparation for a clinical trial.

Methods: Laminectomy of L5-L6 with PMSC-ECM placement directly onto the spinal cord was performed in five fetal lambs at gestational age (GA) 100-106 days.

Placental Mesenchymal Stromal Cells: Preclinical Safety Evaluation for Fetal Myelomeningocele Repair.

Background: Myelomeningocele (MMC) is the congenital failure of neural tube closure in utero, for which the standard of care is prenatal surgical repair. We developed clinical-grade placental mesenchymal stromal cells seeded on a dural extracellular matrix (PMSC-ECM), which have been shown to improve motor outcomes in preclinical ovine models. To evaluate the long-term safety of this product prior to use in a clinical trial, we conducted safety testing in a murine model.

Efficacy of clinical-grade human placental mesenchymal stromal cells in fetal ovine myelomeningocele repair.

Background: While fetal repair of myelomeningocele (MMC) revolutionized management, many children are still unable to walk independently. Preclinical studies demonstrated that research-grade placental mesenchymal stromal cells (PMSCs) prevent paralysis in fetal ovine MMC, however this had not been replicated with clinical-grade cells that could be used in an upcoming human clinical trial. We tested clinical-grade PMSCs seeded on an extracellular matrix (PMSC-ECM) in the gold standard fetal ovine model of MMC.

Placental Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Myelin Regeneration in an Animal Model of Multiple Sclerosis.

Mesenchymal stem/stromal cells (MSCs) display potent immunomodulatory and regenerative capabilities through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EVs). These functional properties of MSCs make them ideal candidates for the treatment of degenerative and inflammatory diseases, including multiple sclerosis (MS). MS is a heterogenous disease that is typically characterized by inflammation, demyelination, gliosis and axonal loss.

In utero treatment of myelomeningocele with placental mesenchymal stromal cells - Selection of an optimal cell line in preparation for clinical trials.

Background: We determined whether in vitro potency assays inform which placental mesenchymal stromal cell (PMSC) lines produce high rates of ambulation following in utero treatment of myelomeningocele in an ovine model.

Methods: PMSC lines were created following explant culture of three early-gestation human placentas. In vitro neuroprotection was assessed with a neuronal apoptosis model.

Spinal Angulation: A Limitation of the Fetal Lamb Model of Myelomeningocele.

Introduction: The surgically induced fetal lamb model is the most commonly used large animal model of myelomeningocele (MMC) but is subject to variation due to surgical technique during defect creation.

Material And Methods: Thirty-one fetal lambs underwent creation of the MMC defect, followed by defect repair with either an extracellular matrix (ECM) patch (n = 10) or ECM seeded with placental mesenchymal stromal cells (n = 21). Postnatal hindlimb function was assessed using the Sheep Locomotor Rating (SLR) scale.

High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele.

Purpose: The purpose of this study was to determine whether seeding density of placental mesenchymal stromal cells (PMSCs) on extracellular matrix (ECM) during in utero repair of myelomeningocele (MMC) affects motor function and neuronal preservation in the ovine model.

Methods: MMC defects were surgically created in 33 fetuses and repaired following randomization into four treatment groups: ECM only (n = 10), PMSC-ECM (42 K cells/cm) (n = 8), PMSC-ECM (167 K cells/cm) (n = 7), or PMSC-ECM (250-300 K cells/cm) (n = 8). Motor function was evaluated using the Sheep Locomotor Rating Scale (SLR).