The Management of Myelomeningocele Study: full cohort 30-month pediatric outcomes.

Myelomeningocele (MMC) is the most frequently occurring congenital abnormality of the central nervous system and leads to significant physical disabilities. Historically treatment involved postnatal closure with management of the associated sequelae including ventricular shunting. The mechanism of neurologic damage that begins with abnormal neurulation followed by continued injury over the course of gestation made MMC a plausible candidate for in-utero surgical repair. Animal and early human studies demonstrated the feasibility of fetal closure. The benefit of in-utero closure was debated until the results of the prospective randomized multicenter Management of Myelomeningocele Study (MOMS trial) were published, demonstrating a decreased need for shunting, reversal of hindbrain herniation, and better neurologic function in the prenatal repair group compared to postnatal repair with maternal complications and prematurity as a trade-off. As such, fetal MMC closure has become a standard of care option for prenatally diagnosed spina bifida. This paper reviews the MOMS trial and the journey of fetal MMC closure since that time.

Fetal surgery for myelomeningocele: After the Management of Myelomeningocele Study (MOMS).

The amniotic fluid has been identified as an untapped source of cells with broad potential, which possess immunomodulatory properties and do not have the ethical and legal limitations of embryonic stem cells. CD117(c-Kit)+ cells selected from amniotic fluid have been shown to differentiate into cell lineages representing all three embryonic germ layers without generating tumors, making them ideal candidates for regenerative medicine applications. Moreover, their ability to engraft in injured organs and modulate immune and repair responses of host tissues, suggest that transplantation of such cells may be useful for the treatment of various degenerative and inflammatory diseases. Although significant questions remain regarding the origin, heterogeneous phenotype, and expansion potential of amniotic fluid stem cells, evidence to date supports their potential role as a valuable stem cell source for the field of regenerative medicine. Stem Cells 2017;35:1663–1673

https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/stem.2553

Concise Review: Amniotic Fluid Stem Cells: The Known, the Unknown, and Potential Regenerative Medicine Applications

Trans-amniotic stem cell therapy (TRASCET) minimizes Chiari-II malformation in experimental spina bifida.

The discovery of mesenchymal stem cells (MSCs) in perinatal sources, such as the amniotic fluid (AF) and the umbilical connective tissue, the so-called Wharton's jelly (WJ), has transformed them into promising stem cell grafts for the application in regenerative medicine. The advantages of AF-MSCs and WJ-MSCs over adult MSCs, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), include their minimally invasive isolation procedure, their more primitive cell character without being tumourigenic, their low immunogenicity and their potential autologous application in congenital disorders and when cryopreserved in adulthood. This chapter gives an overview of the biology of AF-MSCs and WJ-MSCs, and their regenerative potential based on the results of recent preclinical and clinical studies. In the end, open questions concerning the use of WJ-MSCs and AF-MSCs in regenerative medicine will be emphasized.

John Patrick Connors

Papers

Partial or complete coverage of experimental spina bifida by simple intra-amniotic injection of concentrated amniotic mesenchymal stem cells

A comparison between placental and amniotic mesenchymal stem cells for transamniotic stem cell therapy (TRASCET) in experimental spina bifida.

Transamniotic stem cell therapy (TRASCET) mitigates bowel damage in a model of gastroschisis.

Transamniotic stem cell therapy (TRASCET) in a leporine model of gastroschisis.

Extraluminal helicoidal stretch (Helixtretch): A novel method of intestinal lengthening