Division of Neonatology, Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO 64108, USA.
Cells. 2021 Feb 3;10(2):312. doi: 10.3390/cells10020312.
The intestine is extremely dynamic and the epithelial cells that line the intestine get replaced every 3-5 days by highly proliferative intestinal stem cells (ISCs). The instructions for ISCs to self-renew or to differentiate come as cues from their surrounding microenvironment or their niche. A small number of evolutionarily conserved signaling pathways act as a critical regulator of the stem cells in the adult intestine, and these pathways are well characterized. However, the mechanisms, nutritional, and environmental signals that help establish the stem cell niche in the neonatal intestine are less studied. Deciphering the key signaling pathways that regulate the development and maintenance of the stem cells is particularly important to understanding how the intestine regenerates from necrotizing enterocolitis, a devastating disease in newborn infants characterized by inflammation, tissues necrosis, and stem cell injury. In this review, we piece together current knowledge on morphogenetic and immune pathways that regulate intestinal stem cell in neonates and highlight how the cross talk among these pathways affect tissue regeneration. We further discuss how these key pathways are perturbed in NEC and review the scientific knowledge relating to options for stem cell therapy in NEC gleaned from pre-clinical experimental models of NEC.
肠道具有极强的动态性，肠道内层的上皮细胞每隔 3-5 天就会被高度增殖的肠干细胞（ISCs）所取代。ISCs 自我更新或分化的指令来自其周围的微环境或其龛位。少数进化上保守的信号通路作为成人肠道中干细胞的关键调节剂，这些通路已得到很好的描述。然而，有助于在新生儿肠道中建立干细胞龛位的机制、营养和环境信号仍研究较少。解析调节干细胞发育和维持的关键信号通路对于理解肠道如何从坏死性小肠结肠炎（NEC）中再生特别重要，NEC 是一种破坏性疾病，其特征为炎症、组织坏死和干细胞损伤。在这篇综述中，我们整合了目前关于形态发生和免疫途径调节新生儿肠道干细胞的知识，并强调了这些途径之间的相互作用如何影响组织再生。我们进一步讨论了 NEC 中这些关键途径如何受到干扰，并回顾了从 NEC 临床前实验模型中获得的关于 NEC 中干细胞治疗选择的科学知识。
