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Purpose of ReviewThe aim of the study is to provide an overview on the possibility of treating congenital disorders prenatally with mesenchymal stromal cells (MSCs).Recent FindingsMSCs have multilineage potential and a low immunogenic profile and are immunomodulatory and more easy to expand in culture. Their ability to migrate, engraft and differentiate, or act via a paracrine effect on target tissues makes MSCs candidates for clinical therapies. Fetal and extra-fetal MSCs offer higher therapeutic potential compared to MSCs derived from adult sources.SummaryMSCs may be safely transplanted prenatally via ultrasound-guided injection into the umbilical cord. Due to these characteristics, fetal MSCs are of great interest in the field of in utero stem cell transplantation for treatment of congenital disease.

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Expression of OCT4A is one of the hallmarks of pluripotency, defined as a stem cell’s ability to differentiate into all the lineages of the three germ layers. Despite being defined as non-tumorigenic cells with high translational potential, human mid-trimester amniotic fluid stem cells (hAFSCs) are often described as sharing features with embryonic stem cells, including the expression of OCT4A, which could hinder their clinical potential. To clarify the OCT4A status of hAFSCs, we first undertook a systematic review of the literature. We then performed extensive gene and protein expression analyses to discover that neither frozen, nor fresh hAFSCs cultivated in multipotent stem cell culture conditions expressed OCT4A, and that the OCT4A positive results from the literature are likely to be attributed to the expression of pseudogenes or other OCT4 variants. To address this issue, we provide a robust protocol for the assessment of OCT4A in other stem cells.

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Although initially considered safe for the foetus, lithium has been shown to have teratogenic effects if used during the first trimester of pregnancy. Its use is also associated with a higher than expected frequency of still births and perinatal deaths. Our patient, in whom lithium prophylaxis was considered essential for clinical and social reasons, continued to take lithium without medical supervision throughout her pregnancy and had a still birth. We suggest avoiding the use of lithium at least during the first trimester of pregnancy.

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.