Delorme D, Daniels E
Department of Anatomy, McGill University, Montreal, Que., Canada.
Biol Neonate. 1992;62(5):337-50. doi: 10.1159/000243890.
The normal regulation of primitive hemopoietic stem cells (PHSCS) throughout development involves locally produced factors and humoral factors. While considerable information is available on the effects of candidate hemopoietic growth factors (HGFs) on postnatal hemopoietic tissues, little is known about the regulatory events of developing hemopoietic stem cells within fetal microenvironments. Fetal hemopoiesis represents expanding populations and may be under different regulatory control mechanisms. The microinjection of purified interleukin-3 (IL-3), a candidate HGF, into 13-day-old mouse fetuses via the yolk sac, allowed us to evaluate its effects on morphogenetic events and, more specifically, on fetal liver populations using quantitative in vitro clonal assays for hemopoietic precursors. In view of the sensitivity of fetal development during the early organogenetic period, considerable care was taken to identify the stress effects of the surgical laparotomy and the microinjection procedure. Control studies, required to distinguish stress effects of surgical laparotomy and microinjection, clearly revealed that the fetal liver is a sensitive organ responding with limited tissue disorganization, reduced cellularity and erythropoietic activity, as monitored 24 h after experimental intervention. The microinjection of 15 units of IL-3 promoted a significant expansion of depleted liver hemopoietic-cell populations and had stimulatory effects on the distribution of connective tissue mast cells and absolute cell numbers, including hemopoietic precursors (erythroid, granulocyte, macrophage, megakaryocyte), compared to controls. These studies suggest that (1) fetal liver hemopoiesis is selectively sensitive to maternal stress but has an effective regenerative capacity to maintain essential hemopoiesis in utero, and (2) fetal hemopoietic cells require an ability to respond to IL-3 early in fetal development.
原始造血干细胞（PHSCS）在整个发育过程中的正常调节涉及局部产生的因子和体液因子。虽然关于候选造血生长因子（HGFs）对出生后造血组织的影响已有大量信息，但对于胎儿微环境中发育中的造血干细胞的调节事件却知之甚少。胎儿造血代表不断扩大的细胞群体，可能受不同的调节控制机制支配。通过卵黄囊向13日龄小鼠胎儿微量注射纯化的白细胞介素-3（IL-3，一种候选HGF），使我们能够使用造血前体细胞的定量体外克隆测定法评估其对形态发生事件的影响，更具体地说，是对胎儿肝脏细胞群体的影响。鉴于早期器官发生期胎儿发育的敏感性，我们格外小心地确定手术剖腹术和微量注射程序的应激效应。为区分手术剖腹术和微量注射的应激效应而进行的对照研究清楚地表明，胎儿肝脏是一个敏感器官，在实验干预后24小时监测发现，它会出现有限的组织紊乱、细胞数量减少和红细胞生成活性降低等反应。与对照组相比，注射15单位IL-3促进了耗尽的肝脏造血细胞群体的显著扩增，并对结缔组织肥大细胞的分布和绝对细胞数量产生刺激作用，包括造血前体细胞（红系、粒系、巨噬细胞、巨核细胞）。这些研究表明：（1）胎儿肝脏造血对母体应激具有选择性敏感性，但具有有效的再生能力以维持子宫内的基本造血；（2）胎儿造血细胞在胎儿发育早期需要具备对IL-3作出反应的能力。
