Islam A, Glomski C, Henderson E S
Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263.
Anat Rec. 1992 Jul;233(3):440-52. doi: 10.1002/ar.1092330311.
The origin and morphological identity of hematopoietic progenitor cells, as well as their precursor, the pleuripotential hematopoietic stem cell (HSC), has not been established. Our studies of 2 microns sectioned undecalcified plastic-embedded bone marrow (BM) from healthy human fetuses; normal adults; patients with acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic granulocytic leukemia (CGL) in various stages (chronic, accelerated, acute blastic phase, and after autografting); and patients recovering from therapy-induced marrow hypoplasia suggest that proliferative hematopoietic zones exist near the endosteum (endosteal marrow) and the vascular endothelium (capillary and sinus-lining endothelium) and a maturational zone distal to these regions. In some of these areas, morphologically recognizable hematopoietic cells were seen and interpreted as emerging and maturing in a sequential progression, suggesting an origin from the endosteal or endothelial progenitors. In other loci, early hematopoietic cells were seen in close contact with the endosteal or vascular endothelial (VE) cells. This latter relationship suggested that these areas of cellular contact were important and represented sites of cell to cell interaction that may be associated with the liberation of growth factors by endosteal and endothelial cells and their action on hematopoietic progenitor cells. Following treatment-induced hypoplasia, the endosteal and VE cells were seen to modulate, transform, and migrate into the surrounding empty and edematous marrow space as fibroblasts. Later, as hemopoietic regeneration began, clusters of regenerating hematopoietic cells were seen adjacent to bone trabecule (BT) and near the vascular endothelium. We postulate that endosteal and VE cells are the equivalent of embryonal-stage, undifferentiated mesenchyme and, under the appropriate regulatory influence, are capable of modulation and transformation (differentiation) into stromal (fibroblast-like) cells and precursors of hematopoietic cells in normal (physiologic) and stressed (pathologic) conditions. Recently, human endothelial cells have been shown to express a large number of cell surface antigens in common with hematopoietic (myeloid and lymphoid) cells. It is also possible that, in some situations, the VE cells act to establish a microenvironment and liberate growth factor(s), enabling pleuripotential and progenitor cell differentiation into mature hematopoietic cells adjacent to the vascular endothelium. Indeed, vascular endothelium has been shown to elaborate growth factors that participate in normal hematopoiesis.
造血祖细胞及其前体——多能造血干细胞（HSC）的起源和形态特征尚未明确。我们对来自健康人类胎儿、正常成年人、处于不同阶段（慢性期、加速期、急性变期及自体移植后）的急性髓细胞白血病（AML）、急性淋巴细胞白血病（ALL）和慢性粒细胞白血病（CGL）患者，以及从治疗诱导的骨髓发育不全中恢复的患者的2微米厚的未脱钙塑料包埋骨髓（BM）进行了研究，结果表明，增殖性造血区域存在于骨内膜（骨内膜骨髓）和血管内皮（毛细血管和血窦内衬内皮）附近，以及这些区域远端的成熟区域。在其中一些区域，可见形态可辨的造血细胞，并被解释为按顺序逐步出现和成熟，提示其起源于骨内膜或内皮祖细胞。在其他位点，可见早期造血细胞与骨内膜或血管内皮（VE）细胞紧密接触。后一种关系表明，这些细胞接触区域很重要，代表了细胞间相互作用的位点，这可能与骨内膜和内皮细胞释放生长因子及其对造血祖细胞的作用有关。在治疗诱导的发育不全后，可见骨内膜和VE细胞调节、转化并作为成纤维细胞迁移到周围空虚和水肿的骨髓空间。后来，随着造血再生开始，可见再生造血细胞簇邻近骨小梁（BT）并靠近血管内皮。我们推测，骨内膜和VE细胞等同于胚胎期未分化的间充质，在适当的调节影响下，在正常（生理）和应激（病理）条件下能够调节和转化（分化）为基质（成纤维细胞样）细胞和造血细胞前体。最近，已显示人类内皮细胞表达大量与造血（髓系和淋巴系）细胞共有的细胞表面抗原。在某些情况下，VE细胞也有可能起到建立微环境并释放生长因子的作用，使多能和祖细胞在血管内皮附近分化为成熟造血细胞。事实上，已证明血管内皮能分泌参与正常造血的生长因子。
