Islam A, Catovsky D, Goldman J M, Galton D A
Histopathology. 1984 Mar;8(2):293-313. doi: 10.1111/j.1365-2559.1984.tb02343.x.
The interactions between haemopoietic and stromal elements are crucial for stem cell proliferation and differentiation. The bulk of this evidence is derived from experiments in rodents and in-vitro culture studies. We have studied the spatial relationships between the stromal and haemopoietic components and their cellular composition in histological sections of bone marrow (BM) from seven healthy fetuses, 10 normal adults and over 60 patients with acute myeloid leukaemia (AML) and chronic granulocytic leukaemia (CGL) at different stages of the disease. During the early developmental stage (16-18 weeks) fetal BM showed focal haemopoiesis with a characteristic spatial localization of haemopoiesis near bony trabeculae and around small blood vessels. In AML following the treatment-induced hypoplasia, large uniform unilocular fat cells arranged in groups designated 'structured fat' developed from scattered multilocular precursor fat cells. Early foci of haemopoietic regeneration were present almost exclusively in areas of structured fat. In the marrow of patients with CGL in blast transformation (BT) treated by intensive therapy and autografting with cryopreserved haemopoietic stem cells, the haemopoiesis was focal. Clusters of regenerating erythroid precursors or of megakaryocytes were seen in intimate contact with marrow sinusoids and granulopoietic precursors in intimate association with small blood vessels and also in close contact with the endosteal surface of bony trabeculae. We conclude that the endosteal cells, fat cells and the vascular endothelial cells comprise the critical non-haemopoietic stromal elements of human BM. The close associations observed between the regenerating haemopoietic cells and the stromal cells provide strong evidence in support of the existence of a permissive haemopoietic micro-environment in man and emphasize the structural and functional interrelationships that exists between bone, fat, the microvascular system and haemopoiesis in human bone marrow.
造血细胞与基质成分之间的相互作用对于干细胞的增殖和分化至关重要。这些证据大多来自啮齿动物实验和体外培养研究。我们研究了来自7名健康胎儿、10名正常成年人以及60多名处于疾病不同阶段的急性髓性白血病（AML）和慢性粒细胞白血病（CGL）患者的骨髓（BM）组织切片中基质和造血成分之间的空间关系及其细胞组成。在早期发育阶段（16 - 18周），胎儿骨髓显示出局灶性造血，造血具有特征性的空间定位，靠近骨小梁和小血管周围。在AML经治疗诱导的造血功能低下后，由散在的多房性前体脂肪细胞发育而来的成群排列的大而均匀的单房性脂肪细胞，称为“结构化脂肪”。造血再生的早期灶几乎只出现在结构化脂肪区域。在接受强化治疗和冷冻保存的造血干细胞自体移植治疗的CGL急变期（BT）患者的骨髓中，造血是局灶性的。可见再生的红系前体细胞簇或巨核细胞簇与骨髓血窦紧密接触，粒细胞前体细胞与小血管紧密相连，也与骨小梁的骨内膜表面紧密接触。我们得出结论，骨内膜细胞、脂肪细胞和血管内皮细胞构成了人类骨髓关键的非造血基质成分。再生的造血细胞与基质细胞之间观察到的紧密联系为人类存在允许性造血微环境提供了有力证据，并强调了人类骨髓中骨、脂肪、微血管系统和造血之间存在的结构和功能相互关系。
