Patt H M, Maloney M A
Exp Hematol. 1975 Apr;3(2):135-48.
This paper is focused on a mechanically depleted medullary cavity as an experimental model for analysis of marrow regenerative programs. The reconstitution of marrow in an evacuated cavity is basically a local phenomenon in respect to the stimulus for regeneration and the origin of the responsible cells. The nature of the triggering stimulus is unknown, but it is probably related to disruption of the continuity of the marrow stroma and endosteum. The initiating cells appear to be independent lines of mesenchymal and hematopoietic stem cells bound to bone, most likely within the endosteum and haversian system. The mesenchymal cells form the characteristic marrow stroma. Hemic cell regeneration can occur without immigrant hematopoietic stem cells, although such cells are known to contribute to later stages of repopulation. The formation and resorption of trabecular bone appears to be intimately related to the development of a sinusoidal matrix, perhaps by serving as a callus or supporting lattice and perhaps by providing a mechanism for distribution of stromal progenitors. Hematopoiesis is initiated in sites of active bone resorptive. The interplay of events consequent to marrow removal is strikingly similar to that seen with heterotopic marrow implants. Because stromal stem cells, unlike hematopoietic stem cells, do not migrate from distant sites, marrow stroma is the limiting factor in recovery from localized injury. Stromal stem cells are fairly radiosensitive but are not as sensitive as hematopoietic stem cells. The apparent radioresistance of stromal elements in an intact marrow seems to be due to their very low turnover rate. Latent radiation damage can be readily unmasked by conditions that promote their proliferation. This no doubt accounts for the radiosensitivity of stroma in an evacuated femur or heterotopic implant in contrast to its continued functional integrity with similar irradiation of in situ marrow. Even in an intact marrow, however, exposures in the 1000 rad range can lead to slowly evolving hypocellularity associated with diminished blood flow. With higher doses, aplasia of the irradiated site becomes progressively more generalized. It remains to be seen whether this limiting condition is due to the loss of specific regulatory functions or stromal components or merely reflects sinusoidal damage.
本文聚焦于机械性耗尽的髓腔，将其作为分析骨髓再生程序的实验模型。就再生刺激和责任细胞的起源而言，抽空腔隙内骨髓的重建基本上是一种局部现象。触发刺激的性质尚不清楚，但可能与骨髓基质和骨内膜连续性的破坏有关。起始细胞似乎是与骨结合的间充质和造血干细胞的独立谱系，最有可能存在于骨内膜和哈弗斯系统内。间充质细胞形成特征性的骨髓基质。血细胞再生可以在没有造血干细胞迁入的情况下发生，尽管已知此类细胞有助于后期的再填充阶段。小梁骨的形成和吸收似乎与窦状基质的发育密切相关，可能是通过充当骨痂或支撑网架，也可能是通过提供一种间充质祖细胞分布的机制。造血作用起始于活跃的骨吸收部位。骨髓移除后随之发生的一系列事件之间的相互作用与异位骨髓植入时所见的情况惊人地相似。由于与造血干细胞不同，基质干细胞不会从远处迁移，骨髓基质是局部损伤恢复的限制因素。基质干细胞对辐射相当敏感，但不如造血干细胞敏感。完整骨髓中基质成分明显的辐射抗性似乎是由于它们极低的更新率。潜在的辐射损伤很容易被促进其增殖的条件所揭示。这无疑解释了与原位骨髓接受类似照射时仍保持功能完整性相比，抽空股骨或异位植入物中基质的辐射敏感性。然而，即使在完整的骨髓中，1000拉德范围内的照射也会导致与血流减少相关的缓慢进展的细胞减少。剂量更高时，受照射部位的再生障碍会逐渐变得更加普遍。这种限制条件是由于特定调节功能或基质成分的丧失，还是仅仅反映了窦状损伤，仍有待观察。
