1. Academic Validation
  2. Thymopentin enhances the generation of T-cell lineage derived from human embryonic stem cells in vitro

Thymopentin enhances the generation of T-cell lineage derived from human embryonic stem cells in vitro

  • Exp Cell Res. 2015 Feb 15;331(2):387-98. doi: 10.1016/j.yexcr.2014.12.012.
Ming-Xia Zhu 1 Wen-Li Wan 2 Hai-Shen Li 3 Jing Wang 4 Gui-An Chen 5 Xiao-Yan Ke 6
Affiliations

Affiliations

  • 1 Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, PR China; Department of Clinic Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: zhumingxia@bjmu.edu.cn.
  • 2 Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, PR China; Department of Clinic Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: wanwenli110609@126.com.
  • 3 Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: lihaishen.happy@163.com.
  • 4 Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: crystal_bmu@163.com.
  • 5 Department of Reproductive Medical Center, Peking University Third Hospital, Beijing 100191, PR China; Department of Clinic Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: Chenguian2008@bjmu.edu.cn.
  • 6 Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, PR China; Department of Clinic Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: xiaoyank@yahoo.com.
Abstract

Thymopentin is a group of biologically active peptide secreted mainly by the epithelial cells of thymic cortex and medulla. Whether it promotes T cells production from human embryonic stem cells(hESCs) in vitro remains an elusive issue. In the present study, we develop a novel strategy that enhances T-cell lineage differentiation of hESCs in collagen matrix culture by sequential cytokine cocktails treatment combined with thymopentin stimulation. We observed that approximately 30.75% cells expressed CD34 on day 14 of the cultures and expressed the surface markers of erythroid, lymphoid and myeloid lineages. The results of colony assays and gene expressions by RT-PCR analysis also demonstrated that hematopoietic progenitor cells (HPCs) derived from hESCs were capable of multi-lineage differentiation. Further study revealed that culturing with thymopentin treatment, the CD34(+)CD45RA(+)CD7(+) cells sorted from HPCs expressed T-cell-related genes, IKAROS, DNTT, TCRγ and TCRβ, and T-cell surface markers, CD3, cytoplasmic CD3, CD5, CD27, TCRγδ, CD4 and CD8. The differentiated cells produced the cytokines including IFN-γ, IL-2 and TNF-α in response to stimulation, providing the evidence for T-cell function of these cells. In conclusion, thymopentin enhances T-cell lineage differentiation from hESCs in vitro by mimicking thymus peptide environment in vivo.

Keywords

Cell differentiation; Hematopoietic progenitor cells; Human embryonic stem cells\; T lymphocytes; Thymopentin.

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