Gibson L F, Fortney J, Landreth K S, Piktel D, Ericson S G, Lynch J P
Department of Pediatrics, West Virginia University Health Sciences Center, Morgantown 26506, USA.
Biol Blood Marrow Transplant. 1997 Aug;3(3):122-32.
Long-term deficits in hematopoietic reconstitution following aggressive chemotherapeutic regimens used before transplantation may be a result, in part, of damage to the bone marrow microenvironment. Disruption of the hematopoietic microenvironment is indicated by delays in functional recovery of the immune system in spite of delivery of healthy peripheral blood or bone marrow progenitor cells. Cultures of primary human bone marrow stromal cells and a cloned murine stromal cell line, S10, were evaluated for functional changes following in vitro exposure to the chemotherapeutic agent, etoposide (VP-16). Stromal cells had reduced capacity to support lymphoid or myeloid cell proliferation following chemotherapy treatment. A consistent reduction of vascular cell adhesion molecule-1 (VCAM-1) on bone marrow stromal cells also followed VP-16 exposure. These observations indicate that functional disruption of the bone marrow microenvironment by chemotherapeutic regimens must be considered when attempting to optimize patient recovery from hematopoietic transplantation.
移植前使用的强化化疗方案导致的长期造血重建缺陷，可能部分是骨髓微环境受损的结果。尽管输入了健康的外周血或骨髓祖细胞，但免疫系统功能恢复延迟表明造血微环境受到了破坏。对原代人骨髓基质细胞和克隆的小鼠基质细胞系S10进行培养，评估其在体外暴露于化疗药物依托泊苷（VP - 16）后的功能变化。化疗处理后，基质细胞支持淋巴细胞或髓细胞增殖的能力降低。VP - 16暴露后，骨髓基质细胞上的血管细胞黏附分子-1（VCAM - 1）也持续减少。这些观察结果表明，在试图优化患者从造血移植中的恢复时，必须考虑化疗方案对骨髓微环境的功能破坏。
