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Spleen Regulates Hematopoietic Stem/Progenitor Cell Functions Through Regulation of EGF in Cirrhotic Hypersplenism

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Abstract

Background

Hematopoietic abnormality is a common cause of cirrhotic hypersplenism (CH) complications and death; it causes serious adverse effects and is associated with bleeding, anemia, infection in CH patients. However, the underlying mechanism is unclear.

Aims

We aimed to investigate the effects of the spleen on hematopoiesis and hematopoietic stem/progenitor cells (HSPCs) in CH patients.

Methods

Eleven CH patients were enrolled to assess the effects of the spleen on HSPC functions. Hematopoietic changes were examined by flow cytometry analysis. HSPC functions were detected with colony-forming assays and in vitro cell cultures. Enzyme-linked immunosorbent assay (ELISA) was used to test the concentration of epithelial growth factor (EGF).

Results

The number of HSPCs was decreased in CH patients and was rescued after splenectomy. Serum from CH patients dysregulated HSPCs function, and serum from splenectomy patients restored the dysregulated HSPC function in vitro. The concentration of EGF was decreased in CH patients and was restored to normal level after splenectomy. EGF rescued the dysregulated HSPCs function in vitro.

Conclusions

The spleen can regulate the functions of HSPCs in CH patients by regulating EGF signaling. EGF may be a therapeutic target for CH treatment.

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Funding

This study was supported by the Special Fund for Scientific Research of Doctoral Programs in Colleges and Universities, Ministry of Education of China (No. 20110201110050), the National Natural Science Foundation of China (Nos. 91442122, 81600100), Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1171), Young Science and Technology Star Project of Shaanxi Province (No. 2014KJXX-31) and Xi’an Science and Technology Project (No. SF1025 (3)).

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Authors and Affiliations

  1. National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an, 710004, Shaanxi Province, China

    Peijun Wang, Zhenzhen Li, Jiangwei Li, Jun Yang, Guangyao Kong, An Jiang & Zongfang Li

  2. Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi’an, 710004, Shaanxi Province, China

    Peijun Wang, Song Ren, Jiangwei Li, Jun Yang, Guangyao Kong, An Jiang & Zongfang Li

  3. Department of Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, Shaanxi Province, China

    Peijun Wang, Song Ren, Jiangwei Li, Jun Yang, Guangyao Kong, An Jiang & Zongfang Li

Authors
  1. Peijun Wang
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  2. Zhenzhen Li
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  3. Song Ren
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  4. Jiangwei Li
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  5. Jun Yang
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  6. Guangyao Kong
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  7. An Jiang
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  8. Zongfang Li
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Contributions

PW and ZL analyzed the data; PW, JY, and AJ wrote the paper; PW, ZL, JL, and SR performed the research; ZL and AJ designed the research; GK and JL contributed new reagents or analytic tools.

Corresponding authors

Correspondence to Guangyao Kong, An Jiang or Zongfang Li.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The publication of this manuscript has been reviewed and approved by the Second Affiliated Hospital affiliated to Xi’an Jiaotong University Institutional Review Board.

Informed consent

All patients or their families signed informed consent statements before specimen collection, and were performed according to the approved guidelines.

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Cite this article

Wang, P., Li, Z., Ren, S. et al. Spleen Regulates Hematopoietic Stem/Progenitor Cell Functions Through Regulation of EGF in Cirrhotic Hypersplenism. Dig Dis Sci 63, 1860–1867 (2018). https://doi.org/10.1007/s10620-018-5091-7

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  • DOI: https://doi.org/10.1007/s10620-018-5091-7

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