Int J Biol Sci 2017; 13(5):640-651. doi:10.7150/ijbs.18636

Research Paper

Dual Delivery of NGF and bFGF Coacervater Ameliorates Diabetic Peripheral Neuropathy via Inhibiting Schwann Cells Apoptosis

Rui Li1*, Jianfeng Ma1, 2*, Yanqing Wu3*, Matthew Nangle2, Shuang Zou1, Yiyang Li1, Jiayu Yin1, Yingzheng Zhao1, Helin Xu1, Hongyu Zhang1, Xiaokun Li3, Qing song Ye1, 2✉, Jian Wang4✉, Jian Xiao1✉

1. WZMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, Institute of Stem Cell and Tissue Engineering, School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China;
2. UQ-WMU Joint Research Group for Regenerative Medicine, Oral Health Centre, University of Queensland, Brisbane 4006, Australia;
3. The Institute of Life Sciences, Wenzhou University, Wenzhou 325035, China;
4. Department of Peripheral Neurosurgery, the First Affiliated Hospital Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
* These authors contributed equally to this work.


Diabetic neuropathy is a kind of insidious complications that impairs neural and vascular function and ultimately leads to somatic and visceral denervation. Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are important neurotrophic factors for stimulating angiogenesis and improving peripheral nerve function. Administrating a single factor has good therapeutic effect on diabetic peripheral neuropathy (DPN). However, the short half-life and rapid diffusion of growth factors under physiological conditions limits its clinical applications. Here, we used a biodegradable coacervate, composed of heparin and polycation, to dominate the combined release of bFGF and NGF in a steady fashion. We found this combined growth factors (GFs) coacervate, administered as a single injection, improved motor and sensory functions, restored morphometric structure and decreased apoptosis of Schwann cells in a rat model of prolonged DPN. Similarly the GFs coacervate, as compared with free bFGF and NGF combination, markedly reduced the apoptosis level of a rat Schwann cell line, RSC 96 cells in vitro. We also demonstrated that neuroprotective effects of the GFs coacervate in both rat DPN model and hyperglycemia-induced RSC 96 cell model is likely due to suppression of endocytoplasmic reticulum stress (ERS).

Keywords: diabetic peripheral neuropathy (DPN), schwann cells (SCs), basic fibroblast growth factor (bFGF), nerve growth factor (NGF), coacervate.

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How to cite this article:
Li R, Ma J, Wu Y, Nangle M, Zou S, Li Y, Yin J, Zhao Y, Xu H, Zhang H, Li X, Ye Qs, Wang J, Xiao J. Dual Delivery of NGF and bFGF Coacervater Ameliorates Diabetic Peripheral Neuropathy via Inhibiting Schwann Cells Apoptosis. Int J Biol Sci 2017; 13(5):640-651. doi:10.7150/ijbs.18636. Available from