Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Adv Exp Med Biol. 2020;1237:61-74. doi: 10.1007/5584_2019_416.
Transamniotic stem cell therapy (TRASCET) is a novel prenatal therapeutic alternative for the treatment of congenital anomalies. It is based upon the principle of augmenting the pre-existing biological role of select populations of fetal stem cells for targeted therapeutic benefit. For example, amniotic fluid-derived mesenchymal stem cells (afMSCs) play an integral role in fetal tissue repair, validating the use of afMSCs in regenerative strategies. The simple intra-amniotic delivery of these cells in expanded numbers via TRASCET has been shown to promote the repair of and/or significantly ameliorate the effects associated with major congenital anomalies such as neural tube and abdominal wall defects. For example, TRASCET can induce partial or complete coverage of experimental spina bifida through the formation of a host-derived rudimentary neoskin, thus protecting the spinal cord from further damage secondary to amniotic fluid exposure. Furthermore, TRASCET can significantly reduce the bowel inflammation associated with gastroschisis, a common major abdominal wall defect. After intra-amniotic injection, donor stem cells home to the placenta and the fetal bone marrow in the spina bifida model, suggesting a role for hematogenous cell routing rather than direct defect seeding. Therefore, the expansion of TRASCET to congenital diseases without amniotic fluid exposure, such as congenital diaphragmatic hernia, as well as to maternal diseases, is currently under investigation in this emerging and evolving field of fetal stem cell therapy.
经羊膜腔干细胞治疗(TRASCET)是一种新型的产前治疗选择,可用于治疗先天性畸形。它基于增强选择的胎儿干细胞群体的现有生物学作用的原则,以达到靶向治疗效果。例如,羊水来源的间充质干细胞(afMSCs)在胎儿组织修复中发挥着重要作用,验证了 afMSCs 在再生策略中的应用。通过 TRASCET 以扩增数量将这些细胞简单地经羊膜腔内输注,已被证明可促进修复和/或显著改善与神经管和腹壁缺陷等主要先天性畸形相关的影响。例如,TRASCET 可以通过形成宿主衍生的原始新皮肤来诱导实验性脊柱裂的部分或完全覆盖,从而保护脊髓免受羊水暴露引起的进一步损伤。此外,TRASCET 可以显著减少与先天性腹壁缺陷(如先天性膈疝)相关的肠炎症。在羊膜腔内注射后,供体干细胞归巢到胎盘和脊柱裂模型中的胎儿骨髓,这表明存在血源性细胞路由的作用,而不是直接缺陷播种。因此,在胎儿干细胞治疗这个新兴和不断发展的领域中,TRASCET 正在扩展到无羊水暴露的先天性疾病,如先天性膈疝,以及母体疾病。