Department of Obstetrics & Gynecology, Keio University School of Medicine, Tokyo, Japan.
Department of Obstetrics & Gynecology, Keio University School of Medicine, Tokyo, Japan.
Placenta. 2021 Jan 15;104:247-252. doi: 10.1016/j.placenta.2021.01.009. Epub 2021 Jan 12.
Even in the context of modern medicine, infants with fetal and neonatal neurological diseases such as cerebral palsy and myelomeningocele suffer serious long-lasting impairment due to the irreversible neuronal damage. The promotion of neurologically intact survival in patients with perinatal intractable neurological diseases requires the development of novel strategies. One promising strategy involves the use of human amniotic fluid stem cells (hAFSCs), which have attracted much attention in recent years and are known to exert anti-inflammatory and neuroprotective effects. In recent years, the therapeutic effects of hAFSCs on fetal-neonatal neurological diseases have become evident as per intense research efforts by our group and others. Specifically, hAFSCs administered into the nasal cavity migrated to the brain and controlled local inflammation in a rodent model of neonatal hypoxic-ischemic encephalopathy. In contrast, hAFSCs administered intraperitoneally did not migrate to the brain; they rather formed spheroids in the abdominal cavity, resulting in the suppression of systemic inflammation (including in the brain) via the secretion of anti-inflammatory cytokines in concert with peritoneal macrophages in a rodent model of periventricular leukomalacia. Moreover, studies in a rat model of myelomeningocele suggested that hAFSCs administered in utero secreted hepatocyte growth factor and protected the exposed spinal cord during pregnancy. Importantly, autologous hAFSCs, whose use for fetal-neonatal treatment does not raise ethical issues, can be collected during pregnancy and prepared in sufficient numbers for therapeutic use. This article outlines the results of preclinical research on fetal stem cell therapy, mainly involving hAFSCs, in the context of perinatal neurological diseases.
即使在现代医学的背景下，患有脑瘫和脊髓脊膜膨出等胎儿和新生儿神经疾病的婴儿也会因神经元不可逆转的损伤而遭受严重的长期损害。为患有围产期难治性神经疾病的患者促进神经完整的存活需要开发新的策略。一种有前途的策略涉及使用人羊膜干细胞（hAFSCs），近年来，它们引起了广泛关注，已知具有抗炎和神经保护作用。近年来，我们小组和其他小组的大量研究表明，hAFSCs 对胎儿-新生儿神经疾病的治疗效果明显。具体而言，hAFSCs 鼻腔给药后可迁移至大脑，并控制新生缺氧缺血性脑病啮齿动物模型中的局部炎症。相比之下，腹腔内给药的 hAFSCs 不会迁移到大脑；它们在腹腔内形成球体，通过与腹膜巨噬细胞共同分泌抗炎细胞因子，从而抑制全身炎症（包括大脑），在脑室周围白质软化症的啮齿动物模型中。此外，在脊髓脊膜膨出的大鼠模型中研究表明，宫内给予的 hAFSCs 分泌肝细胞生长因子并在怀孕期间保护暴露的脊髓。重要的是，自体 hAFSCs 可在怀孕期间收集，用于胎儿-新生儿治疗不会引起伦理问题，并且可以大量制备用于治疗。本文概述了围产期神经疾病中胎儿干细胞治疗的临床前研究结果，主要涉及 hAFSCs。
