Marrow stromal stem cells
Marrow stromal stem cells
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DOI：
10.1172/jci10413
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发表时间：
2000-06-01
影响因子：
15.9
通讯作者：
Robey, PG
中科院分区：
文献类型：
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作者：
Bianco, P;Robey, PG
编辑帕梅拉·G·罗贝 (Pamela G. Robey) 出现并开始工作。由这些成骨细胞建立的原始骨领被破骨细胞侵蚀，从而允许血管侵入并形成骨髓腔。血管侵袭将先前在骨膜中分化的成骨细胞作为血管周围细胞带入骨髓腔。然后，血窦的发育（以缓慢的血流和细胞可渗透的内皮壁为特征）允许在血管外环境中播种血源性造血干细胞（HSC），然后与原始基质微环境相互作用。这种相互作用使得造血得以建立；它还可以同时阻止原始基质细胞的进一步成骨分化，从而允许骨髓空间在本来是实心骨的内部发育。最终在骨髓空间内形成连续的细胞网络。它通过散布在造血细胞之间的基质细胞从血管的腔外延伸到骨表面。这解释了骨和骨髓的物理和生物连续性，它们一起形成一个单一的器官——骨-骨髓器官。原始非造血骨髓中的基质细胞看起来很像前成骨细胞，分裂活跃，而造血活跃骨髓的基质细胞处于有丝分裂静止状态，但继续高水平表达成骨细胞标志物碱性磷酸酶 (9)。骨髓腔和骨髓基质的形成需要关键转录因子 cbfa1，它控制成骨分化并驱动骨形成 (10, 11)。在发育过程中，骨髓基质细胞的物理出现位于骨和骨形成细胞的物理出现的下游，当然也是相关转录控制的下游（图1）。在出生后的生物体中，cbfa1 通常（也许一致）在人类或小鼠骨髓基质细胞的克隆和非转化系中表达，但不能预测它们在体内移植后的实际成骨能力 (12)。 cbfa1 在这些相同细胞株中的表达不会阻止向非成骨细胞表型（例如脂肪细胞或软骨细胞）的分化。考虑到成骨分化在时间和发育上优先于骨髓基质细胞的物理出现，这些观察结果表明cbfa1指导的成骨定向发生在骨髓基质细胞个体发育的上游，骨髓基质细胞是成骨细胞的出生后前体。这些细胞保留了 cbfa1 的表达，可能是其成骨起源的遗产，但它们仍然能够进入多种分化途径，并且不致力于专性成骨命运。如果将cbfa1视为成骨定向的主基因，那么骨髓基质细胞就是可逆定向的多能细胞。
Pamela G. Robey, Editor appear and begin to function. The primitive bony collar established by these osteoblasts becomes eroded by osteoclasts to allow vascular invasion and the formation of a marrow cavity. Vascular invasion brings osteogenic cells, which had previously differentiated in the periosteum, into the marrow cavity as perivascular cells. The development of sinusoids (characterized by slow blood flow and cell-permeable endothelial walls) then allows for seeding of the extravascular environment with bloodborne hematopoietic stem cells (HSCs), which then interact with the primitive stromal microenvironment. This interaction permits hematopoiesis to be established; it may also simultaneously arrest further osteogenic differentiation by primitive stromal cells, thus allowing a marrow space to develop within what would otherwise be solid bone. A continuous network of cells is ultimately formed within the marrow space. It extends from the abluminal aspects of blood vessels to bone surfaces through the stromal cells interspersed among hematopoietic cells. This explains the physical and biological continuity of bone and marrow, which together form a single organ—the bone–bone marrow organ. Stromal cells in the primitive nonhematopoietic marrow, which appear much like preosteoblasts, divide actively, whereas stromal cells of hematopoietically active marrow are mitotically quiescent but continue to express the osteoblastic marker alkaline phosphatase at high levels (9). Formation of the marrow cavity and marrow stroma requires the pivotal transcription factor, cbfa1, which controls osteogenic differentiation and drives bone formation (10, 11). In development, the physical emergence of marrow stromal cells lies downstream of the physical emergence of bone and bone-forming cells, and, of course, downstream of the relevant transcriptional control (Figure 1). In postnatal organisms, cbfa1 is commonly, and perhaps consistently, expressed in clones and nontransformed lines of human or murine marrow stromal cells but does not predict their actual osteogenic capacity upon in vivo transplantation (12). Expression of cbfa1 in these same cell strains does not prevent differentiation towards nonosteoblastic phenotypes, such as adipocytes or chondrocytes. Considered along with the temporal and developmental priority of osteogenic differentiation over the physical emergence of marrow stromal cells, these observations suggest that osteogenic commitment directed by cbfa1 occurs upstream of the ontogeny of marrow stromal cells, which are the postnatal precursors of osteogenic cells. These cells retain expression of cbfa1, possibly as a legacy of their osteogenic origins, but they remain capable of entering multiple differentiation pathways and are not committed to an obligate osteogenic fate. If cbfa1 is viewed as a master gene for osteogenic commitment, then marrow stromal cells are reversibly committed and multipotential cells.