From the uterus to the spine

Amniotic fluid stem cells show promise in models of spina bifida

Kelsey Kaustinen
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New research is looking to harness stem cells from amniotic fluid and, in a way, turn it right back to working for fetuses. Specifically, scientists from the Keio University School of Medicine in Tokyo have found that injecting amniotic fluid stem cells can protect the spinal cord in fetuses with a particular kind of spina bifida.
They published their results in a paper titled “In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion,” which appeared in STEM CELLS Translational Medicine.
Spina bifida is a type of neural tube defect. As explained by the U.S. Centers for Disease Control and Prevention, “Spina bifida can happen anywhere along the spine if the neural tube does not close all the way. When the neural tube doesn’t close all the way, the backbone that protects the spinal cord doesn’t form and close as it should. This often results in damage to the spinal cord and nerves.” Of the different types of spina bifida, myelomeningocele (MMC) is the most severe. In this form of the condition, the backbone and spinal canal do not close before birth, and as such, “a sac of fluid comes through an opening in the baby’s back. Part of the spinal cord and nerves are in this sac and are damaged.” This can result in partial or full paralysis, developmental delay, hydrocephalus and problems with bowel/bladder control. One out of every 4,000 children born in the U.S. each year are affected by MMC.
“Despite the poor prognosis associated with MMC, the options for prenatal treatments are still limited,” said Dr. Daigo Ochiai of the Keio University School of Medicine, lead investigator for the study. “Recently, however, cellular therapy delivered to the fetus while in the womb has shown promise for treating birth defects. This led us to investigate whether human amniotic fluid stem cells (hAFSCs) might be used to treat fetal MMC, especially since fetal MMC can be diagnosed during an early stage of pregnancy, and this gives us an opportunity to isolate hAFSCs from those patients and use them for in-utero therapy. To the best of our knowledge, this is the first study to do this.”
The 2016 Stem Cells paper “Concise Review: Amniotic Fluid Stem Cells: The Known, the Unknown, and Potential Regenerative Medicine Applications” reports that amniotic fluid is a rich source of stem cells without the ethical issues surrounding embryonic stem cells, as this fluid can be collected easily during a caesarean section. In addition, amniotic fluid stem cells “can be isolated and expanded easily, and have the ability to differentiate into a various cell types without the risk of tumorigenesis.”
For this recent work, the Keio University research team worked with pregnant rats, treating them to induce fetal MMC and then injecting hAFSCs into each amniotic cavity. All told, they examined 116 rat fetuses, according to Ochiai. Following that, they measured “the exposed area of the spinal cord and hepatocyte growth factor (HGF) levels at the lesion.” What they found was that in the rats treated with hAFSCs, the exposed spinal area was smaller and neuronal damage—such as neurodegeneration and astrogliosis—was reduced. The treated group also presented with upregulated HGF expression and HGF-positive hAFSCs, which the authors noted suggests that “these cells migrated to the lesion and secreted HGF to suppress neuronal damage and induce neurogenesis.”
“The ability to use a cell therapy to treat a condition like spina bifida prenatally with minimal risk to the fetus would be a major advance in treatment,” remarked Dr. Anthony Atala, editor-in-chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “We look forward to seeing the development of this important preclinical research.”
The authors note that “the biological basis for hAFSCs treatment remains to be elucidated” as this research moves forward. They also caution that there are a few limitations, saying that “Serious complications of MMC such as Chiari malformation and bladder/rectal disorders remain to be determined, and the most important problem is that RA-induced MMC rats die immediately after birth, and thus, the long-term outcomes with respect to motor dysfunction cannot be studied. Therefore, we would like to address this question using additional in vivo studies like a surgically created ovine MMC model in future investigations.”

Kelsey Kaustinen

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