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Growth hormone-releasing hormone promotes therapeutic effects of peripheral blood endothelial progenitor cells in ischemic repair

  • Z. Li
  • N. Zhang
  • L. Zhu
  • J. Nan
  • J. Shen
  • Z. Wang
  • Y. LinEmail author
Original Article
  • 25 Downloads

Abstract

Purpose

In peripheral artery disease, blockage of the blood supply to the limbs leads to blood flow attenuation and tissue ischemia. We investigated whether growth hormone-releasing hormone (GHRH) could enhance the biological functions and therapeutic effects of endothelial progenitor cells (EPCs) derived from adult human peripheral blood (PB).

Methods

EPCs were isolated from human PB (PB-EPCs) and cord blood and expanded in vitro. PB-EPCs incubated with or without GHRH were evaluated for proliferation, migration, and angiogenesis capacity and apoptosis rates under oxidative stress conditions. Activation of STAT3 and Akt pathways was evaluated using Western blot. A hind-limb ischemia (HLI) mouse model was used to study the efficacy of GHRH in improving EPC therapy in vivo.

Results

GHRH enhanced the proliferation, migration, and angiogenesis capacity of PB-EPCs and reduced apoptosis under H2O2 stimulation. These beneficial effects were GHRH receptor-dependent and were paralleled by increased phosphorylation of STAT3 and Akt. Transplantation of GHRH-preconditioned EPCs into HLI model mice enhanced blood flow recovery by increasing vascular formation density and enhanced tissue regeneration at the lesion site.

Conclusion

Our studies demonstrate a novel role for GHRH in dramatically improving therapeutic angiogenesis in HLI by enhancing the biological functions of EPCs. These findings support additional studies to explore the full potential of GHRH in augmenting cell therapy for the management of ischemia.

Keywords

Angiogenesis Endothelial progenitor cell Growth hormone-releasing hormone Hind-limb ischemia Peripheral artery disease 

Notes

Acknowledgements

This study was financially supported by Wenzhou Municipal Science and Technology Bureau Foundation (grant # Y20170008 and # Y20170052), Natural Science Foundation of Zhejiang Province (grant # LQ18H090007), and National Natural Science Foundation of China (grant # 81800314).

Funding

This study was funded by Wenzhou Municipal Science and Technology Bureau Foundation (grant # Y20170008), Natural Science Foundation of Zhejiang Province (grant # LQ18H090007), Department of Education of Zhejiang Province (Y201636426), and National Natural Science Foundation of China (grant # 81800314).

Compliance with ethical standards

Conflict of interest

The authors have no commercial, proprietary, or financial interest in the products or companies described in this article.

Ethical approval

The ethics committee of the First Affiliated Hospital of Wenzhou Medical University approved the study (2017-310).

Informed consent

All informed consents were obtained from all subjects according to the protocol approved by the ethics committee of the First Affiliated Hospital of Wenzhou Medical University (2017-310).

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Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  1. 1.Research Institute of Experimental Neurobiology, Department of NeurologyThe First Affiliated Hospital, Wenzhou Medical UniversityWenzhouPeople’s Republic of China
  2. 2.Provincial Key Cardiovascular Research Laboratory, Department of CardiologyThe Second Affiliated Hospital, Zhejiang University School of MedicineHangzhouPeople’s Republic of China
  3. 3.Wenzhou Municipal Key Cardiovascular Research Laboratory, Department of CardiologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouPeople’s Republic of China

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