Stem cell therapy combined with an open intrauterine surgery of myelomeningocele in fetal sheep improves motor function and preserves neurons in the spinal cord.

• Applicant: Professor Dr. Christian Bamberg
• Subject Area: Gynaecology and Obstetrics
• Term: from 2022 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 502665298

Myelomeningocele (MMC) is the most severe form of spina bifida and is the commonest congenital malformation of the central nervous system. About 1 in every 2.000 pregnancies in the EU are affected. In Germany 65- 90% of parents opted for a termination of pregnancy after prenatal diagnosis. MMC is one of the most complex congenital birth defect which results in substantial morbidity. Depending on the level (90% lumbosacral) and size of the lesion children born with MMC have a variety of burdens such as paralysis and sensory dysfunction below the affected spine level, bladder and bowel incontinence, brain abnormalities (hydrocephalus and shunting in 90%), cognitive impairment, mental retardation and seizures. There is increasing evidence in animal models that local administration of stem cells, in particular Mesenchymal Stromal Cells (MSC), combined with a prenatal repair of MMC preserves spinal cord function. Therefore the remarkable regenerative capacity of MSC and the prenatal closure of MMC offers a novel fetal therapy strategy to further reduce and repair the sustained spinal cord damage in a serious disease. A patented method to isolate MSC from umbilical cord tissue from healthy newborns at high quantity and GMP quality is used (Desacell.®. )Fetal MMC (n=11 sheep) defect will be surgical created at gestational age 75 days. Fetuses will be 1:2 randomized to prenatal repair 25 days after MMC creation with or without local MSC application. At gestational age 145 days the lambs will be delivered by c-section.The aims of this study are threefold:1. The local administration of MSC (Desacell® is feasible and improves motor function (evaluated by the "sheep locomotor rating scale"). 2. Cross-sectional areas of spinal cord and gray matter are significantly higher after prenatal MMC + MSC therapy in comparison with MMC therapy only.3. Large neurons density is significantly correlated with the motor function after MSC application.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Konrad Reinshagen