Research Paper Volume 12, Issue 1 pp 106—121

Endothelial progenitor cells promote viability and nerve regenerative ability of mesenchymal stem cells through PDGF-BB/PDGFR-β signaling

Jiafeng Fang1, *, , Xuna Huang2, *, , Xiaoyan Han2, , Zongheng Zheng1, , Cheng Hu3, , Tufeng Chen1, , Xiaofeng Yang1, , Xi Ouyang1, , Zehong Chen1, , Hongbo Wei1, ,

  • 1 Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • 2 Central Laboratory, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • 3 Department of Urinary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
* Equal contribution

Received: May 7, 2019       Accepted: December 5, 2019       Published: January 3, 2020
How to Cite

Copyright: © 2020 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Denervation-induced erectile dysfunction (ED) is a prevailing health problem. Our previous study revealed that endothelial progenitor cells (EPCs) promoted the effect of mesenchymal stem cells (MSCs) on restoration of denervation-induced ED in rats. However, underling mechanisms are still largely elusive. In this study, EPCs and MSCs were co-cultured and resorted to co-EPCs and co-MSCs. EPCs-derived paracrine factors containing PDGF-BB (platelet-derived growth factor) were detected, and MSCs were pre-treated with PDGF-BB, while co-MSCs were pre-treated with PDGFR inhibitor AG1296. Either viability or nerve regenerative ability of MSCs was evaluated. In addition, inhibition of either PI3K/Akt or MEK/Erk pathway was performed to evaluate the role of PI3K/Akt and MEK/Erk pathway in PDGF-BB-induced viability of MSCs. The results revealed that PDGF-BB significantly increased the proportion of PDGFR-β+ MSCs, and promoted both in-vitro and in-vivo viability, as well as nerve regenerative capacity and erectile function restoration of MSCs in rats. Inhibition of PI3K/Akt, MEK/Erk pathway or mTOR led to decrease of PDGF-BB/PDGFR-β induced viability of MSCs. To our knowledge, our study first demonstrates that EPCs promote viability and potential nerve regenerative ability of MSCs through PDGF-BB/PDGFR-β signaling and its downstream PI3K/Akt and MEK/Erk pathways. mTOR acts as a co-mediator in PI3K/Akt and MEK/Erk pathways.


bFGF: basic fibroblast growth factor; bFGFR: basic fibroblast growth factor receptor; CEBPα: CCAAT-enhancer binding protein alpha; CN: cavernous nerve; CNI: cavernous nerve injury; ED: erectile dysfunction; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EPCs: endothelial progenitor cells; FABP4: fatty acid binding protein 4; HB-EGF: heparin binding epidermal growth factor; ICP: intracavernous pressure; PDGF: platelet-derived growth factor; PDGFR: platelet-derived growth factor receptor; RUNX2: runt-related transcription factor 2; PPARγ: peroxisome proliferator activated receptor; MAP: mean arterial pressure; MAP2: microtubule associated protein 2; mICP: maximal intracavernous pressure; MPG: major pelvic ganglia; MSCs: mesenchymal stem cells; tICP: total intracavernous pressure; TUBB3: tubulin beta 3.