Ghavamzadeh Ardeshir, Sotoudeh Masoud, Hashemi Taheri Amir Pejman, Alimoghaddam Kamran, Pashaiefar Hossein, Jalili Mahdi, Shahi Farhad, Jahani Mohammad, Yaghmaie Marjan
Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Kargar Shomali Ave, Shariati Hospital, Tehran, Iran.
Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Ann Hematol. 2018 Feb;97(2):327-334. doi: 10.1007/s00277-017-3181-9. Epub 2017 Nov 17.
The aims of this study are to determine the replacement rate of damaged hepatocytes by donor-derived cells in sex-mismatched recipient patients with thalassemia major and to determine whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells (HSCs) can alleviate liver fibrosis. Ten sex-mismatched donor-recipient pairs who received co-transplantation of HSCs with mesenchymal stem cells were included in our study. Liver biopsy was performed before transplantation. Two other liver biopsies were performed between 2 and 5 years after transplantation. The specimens were studied for the presence of donor-derived epithelial cells or hepatocytes using fluorescence in situ hybridization by X- and Y-centromeric probes and immunohistochemical staining for pancytokeratin, CD45, and a hepatocyte-specific antigen. All sex-mismatched tissue samples demonstrated donor-derived hepatocyte independent of donor gender. XY-positive epithelial cells or hepatocytes accounted for 11 to 25% of the cells in histologic sections of female recipients in the first follow-up. It rose to 47-95% in the second follow-up. Although not statistically significant, four out of ten patients showed signs of improvement in liver fibrosis. Our results showed that co-transplantation of HSC with mesenchymal stem cells increases the rate of replacement of recipient hepatocytes by donor-derived cells and may improve liver fibrosis.
本研究的目的是确定在重型地中海贫血的性别不匹配受体患者中，供体来源的细胞对受损肝细胞的替代率，并确定间充质干细胞和造血干细胞（HSC）的联合移植是否能减轻肝纤维化。我们的研究纳入了10对接受HSC与间充质干细胞联合移植的性别不匹配供受体对。在移植前进行肝活检。在移植后2至5年期间进行另外两次肝活检。使用X和Y着丝粒探针通过荧光原位杂交以及针对全细胞角蛋白、CD45和肝细胞特异性抗原的免疫组织化学染色，对标本进行供体来源的上皮细胞或肝细胞检测。所有性别不匹配的组织样本均显示存在供体来源的肝细胞，且与供体性别无关。在首次随访中，XY阳性上皮细胞或肝细胞在女性受体组织学切片的细胞中占11%至25%。在第二次随访中，这一比例升至47% - 95%。虽然无统计学意义，但10名患者中有4名显示出肝纤维化改善的迹象。我们的结果表明，HSC与间充质干细胞的联合移植可提高供体来源的细胞对受体肝细胞的替代率，并可能改善肝纤维化。
