Myelomeningocele is a severe congenital defect in which the backbone plus spinal canal do not close before birth, putting those people affected at risk of lifelong neurological problems. In a preclinical research published June 6th in Stem Cellular Reports , researchers developed a stem cell-based treatment for generating skin grafts to cover myelomeningocele defects just before birth. They first generated artificial skin from human being induced pluripotent stem cells (iPSCs), and then successfully transplanted the skin grafts into rat fetuses with myelomeningocele.

“We provide preclinical proof of idea for a fetal therapy that could improve outcomes and prevent long term complications associated with myelomeningocele — one of the most severe birth defects, inch says senior study author Akihiro Umezawa of Japan’s National Research Institute for Child Health and Development. “Since our fetal cell treatment is minimally invasive, they have the potential to become a much-needed novel treatment for myelomeningocele. inch

Myelomeningocele, which is the most serious and typical form of spina bifida, is a neural tube defect where the bones of the spine do not completely form. As a result, areas of the spinal cord and nerves come through the open section of the spine. A baby born with this disorder typically has an open up area or a fluid-filled sac on the mid to lower back again. Most children with this condition are at risk of mind damage because too much fluid builds up in their brains. In addition they often experience symptoms such as loss of bladder or intestinal control, loss of feeling in the legs or feet, plus paralysis of the legs.

Babies born along with myelomeningocele usually undergo surgery to repair the defect inside the first few days of life. Some highly specialized facilities also offer intrauterine surgery to close the defect prior to the baby is born. Although prenatal surgery can improve later on neurological outcomes compared with postnatal surgery, it is also associated with increased rates of preterm birth and other serious complications, underscoring the need for safe and effective fetal therapies.

To address this issue, Umezawa and his team set out to develop a minimally invasive technique for generating and transplanting skin grafts that could protect large myelomeningocele defects earlier during pregnancy, potentially improving long lasting outcomes while reducing surgical risks. In particular, they were thinking about using iPSC technology, which involves genetically reprogramming patients’ tissues to an embryonic stem cell-like state and then converting these types of immature cells into specialized cell types found in various areas of the body. This approach avoids ethical concerns while offering the advantages of the potentially unlimited source of various cell types for hair transplant, as well as minimal risk of graft rejection by the defense mechanisms.

In the new study, the researchers very first generated human iPSCs from fetal cells taken from amniotic fluid from two pregnancies with severe fetal illness (Down syndrome and twin-twin3 transfusion syndrome). They then utilized a chemical cocktail in a novel protocol to turn the particular iPSCs into skin cells and treated these tissue with additional compounds such as epidermal growth factor to market their growth into multi-layered skin. In total, it got approximately 14 weeks from amniotic fluid preparation in order to 3D skin generation, which would allow for transplantation to be carried out in humans during the therapeutic window of 28-29 days of gestation.

Next, the researchers transplanted the 3D skin grafts into 20 rat fetuses through a small incision in the uterine wall. The synthetic skin partially covered the myelomeningocele defects in 8 of the newborn rats and completely covered the flaws in four of the newborn rats, protecting the spinal-cord from direct exposure to harmful chemicals in the external atmosphere. Moreover, the engrafted 3D skin regenerated with the development of the fetus and accelerated skin coverage throughout the being pregnant period. Notably, the transplanted skin cells did not result in tumor formation, but the treatment significantly decreased birth bodyweight and body length.

“We are motivated by our results and believe that our fetal originate cell therapy has great potential to become a novel therapy for myelomeningocele, ” Umezawa says. “However, additional research in larger animals are needed to demonstrate that our fetal originate cell therapy safely promotes long-term skin regeneration plus neurological improvement. ”

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