2. Academic Validation
  3. Sulfated polysaccharide directs therapeutic angiogenesis via endogenous VEGF secretion of macrophages

Sulfated polysaccharide directs therapeutic angiogenesis via endogenous VEGF secretion of macrophages

  • Sci Adv. 2021 Feb 10;7(7):eabd8217. doi: 10.1126/sciadv.abd8217.
Yuanman Yu 1,  Kai Dai 1,  Zehua Gao 2,  Wei Tang 3,  Tong Shen 2,  Yuan Yuan 2,  Jing Wang 4,  Changsheng Liu 5
Affiliations

Affiliations

  • 1 The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.
  • 2 Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, P. R. China.
  • 3 Shenzhen Key Laboratory of Nanobiomechanics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China.
  • 4 The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China. biomatwj@163.com liucs@ecust.edu.cn.
  • 5 Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, P. R. China. biomatwj@163.com liucs@ecust.edu.cn.
PMID: 33568481 DOI: 10.1126/sciadv.abd8217
Abstract

Notwithstanding the remarkable progress in the clinical treatment of ischemic disease, proangiogenic drugs mostly suffer from their abnormal angiogenesis and potential Cancer risk, and currently, no off-the-shelf biomaterials can efficiently induce angiogenesis. Here, we reported that a semisynthetic sulfated chitosan (SCS) readily engaged anti-inflammatory macrophages and increased its secretion of endogenous vascular endothelial growth factor (VEGF) to induce angiogenesis in ischemia via a VEGF-VEGFR2 signaling pathway. The depletion of host macrophages abrogated VEGF secretion and vascularization in implants, and the inhibition of VEGF or VEGFR2/KDR/Flk-1 signaling also disrupted the macrophage-associated angiogenesis. In addition, in a macrophage-inhibited mouse model, SCS efficiently helped to recover the endogenous levels of VEGF and the number of CD31hiEmcnhi vessels in ischemia. Thus, both sulfated group and pentasaccharide sequence in SCS played an important role in directing the therapeutic angiogenesis, indicating that this highly bioactive biomaterial can be harnessed to treat ischemic disease.

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