Stein Jerry, Yaniv Isaac, Askenasy Nadir
Frankel Laboratory of Experimental Bone Marrow Transplantation, Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Folia Histochem Cytobiol. 2005;43(4):191-5.
Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic cells with the bone marrow stroma evolves as the most important early event. Adhesion to the marrow, rather than the vascular endothelium, determines the efficiency of both homing and seeding, and is absolutely essential to maintain cell viability in the marrow. Seeding and engraftment may be improved either by bypassing homing or by localized transplant of a large number of cells in a relatively small marrow space. There is functional redundancy in the molecular pathways that mediate the cell-stroma interaction, such that blockage of a single pathway has only minor effect on homing and seeding. We hypothesize that successfully seeding-engrafting cells undergo extensive phenotypic changes as a consequence of interaction with the stroma, without engaging in rapid proliferation. Surprisingly, Fas-ligand appears to promote hematopoietic cell engraftment by immunomodulatory and trophic effects.
持久的造血干细胞植入需要有效地归巢至受体骨髓并在其中定植。通过对功能植入研究进行回顾性分析来剖析细胞和分子机制，对理解这一过程的早期阶段造成了严重限制。我们已经建立了一种实验方法，可在受体骨髓水平实时对标记细胞进行体内功能成像。造血细胞与骨髓基质的黏附相互作用是最重要的早期事件。与骨髓而非血管内皮的黏附决定了归巢和定植的效率，并且对于维持细胞在骨髓中的活力绝对至关重要。通过绕过归巢或在相对较小的骨髓空间内局部移植大量细胞，可改善定植和植入。介导细胞-基质相互作用的分子途径存在功能冗余，因此阻断单一途径对归巢和定植仅有轻微影响。我们推测，成功定植-植入的细胞由于与基质相互作用而经历广泛的表型变化，而无需快速增殖。令人惊讶的是，Fas配体似乎通过免疫调节和营养作用促进造血细胞植入。
