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Co-transplantation of Hematopoietic Stem Cells and Cxcr4 Gene-Transduced Mesenchymal Stem Cells Promotes Hematopoiesis

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Abstract

Mesenchymal stem cells (MSCs) are a promising candidate for cellular therapies. Co-transplantation of MSCs and hematopoietic stem cells (HSCs) promotes successful engraftment and improves hematopoietic recovery. In this study, the effects of co-transplantation of HSCs and mouse bone marrow (BM)-derived MSCs overexpressing CXCR4 (CXCR4-MSC) on CXCR4-MSC homing capacity and the reconstitution potential in lethally irradiated mice were evaluated. Recovery of donor-derived peripheral blood leukocytes and platelets was accelerated when CXCR4-MSCs were co-transplanted with BM cells. The frequency of c-kit+Sca+Lin− HSCs was higher in recipient BM following co-transplantation of CXCR4-MSCs compared with the EGFP-MSC control and the BMT only groups. Surprisingly, the rate of early engraftment of donor-derived BM cells in recipients co-transplanted with CXCR4-MSCs was slightly lower than in the absence of MSCs on day 7. Moreover, co-transplantation of CXCR4-MSCs regulated the balance of T helper cells subsets. Hematopoietic tissue reconstitution was evaluated by histopathological analysis of BM and spleen. Co-transplantation of CXCR4-MSCs was shown to promote the recovery of hematopoietic organs. These findings indicate that co-transplantation of CXCR4-MSCs promotes the early phase of hematopoietic recovery and sustained hematopoiesis.

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Acknowledgments

The authors acknowledge CuiPing Zhang, GuoLiang Song, and Chong Chen for technical assistance. This manuscript was proofread by a native English professional with science background at Elixigen Corporation. This work was supported by grants from the National Natural Science Foundation of China (No. 81300441), Jiangsu province LiuDaRenCaiGaoFeng project (2013-WSN-080) and Xuzhou Science and Technology Project, China (No. XZZD1138).

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Authors and Affiliations

  1. Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, West Huaihai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Wei Chen, Guizhen Su, Yu Zang, Zhiling Yan, Hai Cheng, Bin Pan, Jiang Cao, Qingyun Wu, Kai Zhao, Feng Zhu, Lingyu Zeng, Zhenyu Li & Kailin Xu

  2. Xuzhou Children’s Hospital, Sudi Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Miao Li

  3. Xuzhou Medical College, Blood Diseases Institute, Xuzhou, 221002, People’s Republic of China

    Wei Chen & Kailin Xu

  4. Key Laboratory of Bone Marrow Stem Cell, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Wei Chen & Kailin Xu

Authors
  1. Wei Chen
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  2. Miao Li
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  3. Guizhen Su
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  4. Yu Zang
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  7. Bin Pan
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  8. Jiang Cao
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  10. Kai Zhao
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  11. Feng Zhu
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  12. Lingyu Zeng
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  13. Zhenyu Li
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  14. Kailin Xu
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Corresponding author

Correspondence to Kailin Xu.

Additional information

Wei Chen, Miao Li, and Guizhen Su have contributed equally to this work.

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Chen, W., Li, M., Su, G. et al. Co-transplantation of Hematopoietic Stem Cells and Cxcr4 Gene-Transduced Mesenchymal Stem Cells Promotes Hematopoiesis. Cell Biochem Biophys 71, 1579–1587 (2015). https://doi.org/10.1007/s12013-014-0381-y

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  • DOI: https://doi.org/10.1007/s12013-014-0381-y

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