Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy
Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy
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DOI：
10.1007/s00277-009-0896-2
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发表时间：
2010-07-01
影响因子：
3.5
通讯作者：
Donaldson, Craig
中科院分区：
文献类型：
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作者：
Kemp, Kevin;Morse, Ruth;Donaldson, Craig
治疗血液疾病时大剂量化疗（HDC）后的造血恢复可能缓慢和/或不完全。这通常归因于进行性造血干细胞衰竭，尽管造血功能缺陷可能部分归因于基质功能不良。众所周知，化疗会在体外损伤成熟的骨髓基质细胞，但 HDC 在体内对骨髓间充质干细胞 (MSC) 的损伤程度尚不清楚。为了解决这个问题，对来自未经治疗和接受化疗的血液恶性肿瘤患者的骨髓间充质干细胞的表型和功能特性进行了比较。这项研究表明，来自接受 HDC 方案的患者的 MSC 的 MSC 扩增和 MSC CD44 表达显着减少，因此暗示在化疗预处理患者中使用自体 MSC 进行未来治疗策略的潜在缺点。我们观察到的这些 HDC 引起的缺陷的临床重要性可以通过前瞻性随机试验来确定，这些试验是在有或没有造血干细胞挽救的 HDC 环境下，间充质干细胞共移植对造血恢复的影响。
Hematopoietic recovery after high-dose chemotherapy (HDC) in the treatment of hematological diseases may be slow and/or incomplete. This is generally attributed to progressive hematopoietic stem cell failure, although defective hematopoiesis may be in part due to poor stromal function. Chemotherapy is known to damage mature bone marrow stromal cells in vitro, but the extent to which marrow mesenchymal stem cells (MSCs) are damaged by HDC in vivo is largely unknown. To address this question, the phenotype and functional properties of marrow MSCs derived from untreated and chemotherapeutically treated patients with hematological malignancy were compared. This study demonstrates a significant reduction in MSC expansion and MSC CD44 expression by MSCs derived from patients receiving HDC regimens, thus implicating potential disadvantages in the use of autologous MSCs in chemotherapeutically pretreated patients for future therapeutic strategies. The clinical importance of these HDC-induced defects we have observed could be determined through prospective randomized trials of the effects of MSC cotransplantation on hematopoietic recovery in the setting of HDC with and without hematopoietic stem cell rescue.