Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Kargar Shomali Street, Tehran, 1411713131, Iran.
Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Stem Cell Res Ther. 2021 Mar 29;12(1):213. doi: 10.1186/s13287-021-02242-8.
Hepatic fibrosis is a common complication in transfusion-dependent thalassemia patients. Data on the co-transplantation of mesenchymal stem cells (MSCs) with hematopoietic stem cells (HSCs) in beta-thalassemia major patients are scarce. Therefore, we aimed to evaluate the effect of co-transplantation of bone marrow-derived MSC with HSCs on the liver fibrosis alleviation and transplant outcomes in class III beta-thalassemia major.
Between April 1998 and January 2017, a total of 224 consecutive patients with class III beta-thalassemia major underwent allogeneic HSCT in the Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran. To assess liver fibrotic changes after transplantation, 47 patients participated in the MSC plus HSC group and 30 patients in the HSC only group at the end of the follow-up period. All patients underwent laboratory tests, especially serum ferritin and liver function testing, hepatic T2* MRI, liver biopsy, and FibroScan before and 2 years after transplantation. Kaplan-Meier curves were derived to determine survival and were compared using the log-rank test. Repeated-measure, mixed-effect linear regression models were used to examine the changes in liver fibrosis over time.
The 10-year OS rate was 71.84% in the mesenchymal group and 61.89% in the non-mesenchymal group (P value = 0.294), while the 10-year TFS rate was 63.64% in the mesenchymal group and 52.78% in the non-mesenchymal group (P value = 0.285). No significant difference was observed in the 10-year NRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD between the two groups. In addition, the results of repeated-measure, mixed-effect linear regression models showed that none of the variables determining hepatic fibrosis had a significant difference between patients receiving MSCs and patients who did not receive MSCs.
Based on the results of this study, a single infusion of MSCs at the time of HSCT to patients with class III beta-thalassemia major could not significantly improve the liver fibrosis alleviation and transplantation outcomes, including OS, TFS, TRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD.
肝纤维化是输血依赖型地中海贫血患者的常见并发症。关于β地中海贫血患者造血干细胞（HSCs）与间充质干细胞（MSCs）共移植的数据很少。因此，我们旨在评估骨髓来源的 MSC 与 HSCs 共移植对 III 类β地中海贫血患者肝纤维化缓解和移植结局的影响。
1998 年 4 月至 2017 年 1 月，伊朗德黑兰大学医学科学研究所肿瘤学、血液学和细胞治疗研究所共对 224 例 III 类β地中海贫血患者进行了异基因 HSCT。为了评估移植后肝纤维化的变化，在随访结束时，47 例患者纳入 MSC 加 HSC 组，30 例患者纳入 HSC 仅组。所有患者均进行了实验室检查，尤其是血清铁蛋白和肝功能检查、肝脏 T2*MRI、肝活检和 FibroScan，在移植前和移植后 2 年均进行了这些检查。采用 Kaplan-Meier 曲线确定生存率，并采用对数秩检验进行比较。采用重复测量混合效应线性回归模型来检测肝纤维化随时间的变化。
MSC 组的 10 年 OS 率为 71.84%，非 MSC 组为 61.89%（P 值=0.294），MSC 组的 10 年 TFS 率为 63.64%，非 MSC 组为 52.78%（P 值=0.285）。两组间 10 年 NRM、排斥率、ANC 植入、血小板植入、急性移植物抗宿主病和慢性移植物抗宿主病的差异无统计学意义。此外，重复测量混合效应线性回归模型的结果表明，在接受 MSCs 和未接受 MSCs 的患者中，决定肝纤维化的变量均无显著差异。
根据本研究结果，在 HSCT 时单次输注 MSCs 不能显著改善 III 类β地中海贫血患者的肝纤维化缓解和移植结局，包括 OS、TFS、TRM、排斥率、ANC 植入、血小板植入、急性移植物抗宿主病和慢性移植物抗宿主病。
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