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Liver fibrosis alleviation after co-transplantation of hematopoietic stem cells with mesenchymal stem cells in patients with thalassemia major

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Abstract

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.

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Acknowledgments

This research was supported by the Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences.

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Authors and Affiliations

  1. Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Kargar Shomali Ave, Shariati Hospital, Tehran, Iran

    Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Mahdi Jalili, Mohammad Jahani & Marjan Yaghmaie

  2. Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Masoud Sotoudeh

  3. Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Amir Pejman Hashemi Taheri

  4. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Hossein Pashaiefar

  5. Department of Hematology and Medical Oncology, Cancer Research Center, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

    Farhad Shahi

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  1. Ardeshir Ghavamzadeh
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  2. Masoud Sotoudeh
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  3. Amir Pejman Hashemi Taheri
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Correspondence to Marjan Yaghmaie.

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All procedures were performed according to the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and later amendments or comparable ethical standards. The proposal was approved by the Ethics Committee of Tehran University of Medical Sciences.

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Ghavamzadeh, A., Sotoudeh, M., Hashemi Taheri, A.P. et al. Liver fibrosis alleviation after co-transplantation of hematopoietic stem cells with mesenchymal stem cells in patients with thalassemia major. Ann Hematol 97, 327–334 (2018). https://doi.org/10.1007/s00277-017-3181-9

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