Center for Research in Biomedicine, Faculty of Applied Sciences, University of West of England, Bristol, UK.
Ann Hematol. 2010 Jul;89(7):701-13. doi: 10.1007/s00277-009-0896-2. Epub 2010 Jan 30.
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.
造血恢复后的大剂量化疗（HDC）在治疗血液疾病可能是缓慢的和/或不完整的。这通常归因于进行性造血干细胞衰竭，尽管有缺陷的造血可能部分是由于基质功能不良。化疗是已知的损伤成熟骨髓基质细胞在体外，但骨髓间充质干细胞（MSCs）被大剂量化疗在体内损伤的程度在很大程度上是未知的。为了解决这个问题，从未治疗和接受血液系统恶性肿瘤化疗的患者中分离的骨髓间充质干细胞的表型和功能特性进行了比较。本研究表明，来源于接受 HDC 方案治疗的患者的 MSC 的 MSC 扩增和 MSC CD44 表达显著减少，因此提示在接受化疗预处理的患者中使用自体 MSC 进行未来治疗策略可能存在潜在的不利因素。我们观察到的这些 HDC 诱导的缺陷的临床重要性可以通过前瞻性随机试验来确定，该试验研究了 MSC 共移植对 HDC 联合和不联合造血干细胞挽救治疗后造血恢复的影响。
