Enhanced therapeutic neovascularization by CD31-expressing cells and embryonic stem cell-derived endothelial cells engineered with chitosan hydrogel containing VEGF-releasing microtubes

Sangho Lee, Chandra M. Valmikinathan, Jaemin Byun, Sangsung Kim, Geehee Lee, Nassir Mokarram, S. Balakrishna Pai, Elisa Um, Ravi V. Bellamkonda, Young Sup Yoon

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Various stem cells and their progeny have been used therapeutically for vascular regeneration. One of the major hurdles for cell-based therapy is low cell retention in vivo, and to improve cell survival several biomaterials have been used to encapsulate cells before transplantation. Vascular regeneration involves new blood vessel formation which consists of two processes, vasculogenesis and angiogenesis. While embryonic stem cell (ESC)-derived endothelial cells (ESC-ECs) have clearer vasculogenic potency, adult cells exert their effects mainly through paracrine angiogenic activities. While these two cells have seemingly complementary advantages, there have not been any studies to date combining these two cell types for vascular regeneration. We have developed a novel chitosan-based hydrogel construct that encapsulates both CD31-expressing BM-mononuclear cells (BM-CD31+ cells) and ESC-ECs, and is loaded with VEGF-releasing microtubes. This cell construct showed high cell survival and minimal cytotoxicity in vitro. When implanted into a mouse model of hindlimb ischemia, it induced robust cell retention, neovascularization through vasculogenesis and angiogenesis, and efficiently induced recovery of blood flow in ischemic hindlimbs. This chitosan-based hydrogel encapsulating mixed adult and embryonic cell derivatives and containing VEGF can serve as a novel platform for treating various cardiovascular diseases.

Original languageEnglish
Pages (from-to)158-167
Number of pages10
JournalBiomaterials
Volume63
DOIs
Publication statusPublished - 2015 Sep 1

Bibliographical note

Funding Information:
This work was supported in part by a Wallace H. Coulter Translational Research Grant , NIH grant DP3DK094346 , NHLBI of the NIH as a Program of Excellence in Nanotechnology award HHSN268201000043C, NSF-EBICS grant CBET-0939511 , Faculty Research Assistance Program of Yonsei University College of Medicine 2015 , and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIP) (No. 2015M3A9C6031514 ). We would also like to acknowledge the Robert P. Apkarian Integrated Electron Microscopy Core of Emory University for their help with the electron microscopy of the lipid microtubes.

Publisher Copyright:
© 2015 Elsevier Ltd.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

Fingerprint

Dive into the research topics of 'Enhanced therapeutic neovascularization by CD31-expressing cells and embryonic stem cell-derived endothelial cells engineered with chitosan hydrogel containing VEGF-releasing microtubes'. Together they form a unique fingerprint.

Cite this