Three-dimensional cell grafting enhances the angiogenic efficacy of human umbilical vein endothelial cells

Suk Ho Bhang, Seahyoung Lee, Tae Jin Lee, Wan Geun La, Hee Seok Yang, Seung Woo Cho, Byung Soo Kim

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Despite the great potential of cell therapy for ischemic disease, poor cell survival after engraftment in ischemic tissue limits its efficacy. Here we tested a hypothesis that three-dimensionally grafted human umbilical vein endothelial cell (HUVEC) spheroids would exhibit improved angiogenic efficacy following transplantation into mouse ischemic limbs compared with HUVECs prepared by conventional two-dimensional monolayer culture. One day after surgical induction of hindlimb ischemia in athymic mice, HUVECs cultured in monolayer or HUVEC spheroids were transplanted intramuscularly into ischemic limbs. Four weeks after the treatment, in the spheroid HUVEC transplantation group, we observed increased hypoxia-inducible factor-1α expression, decreased apoptosis, and increased HUVEC survival in the ischemic tissue compared with the monolayer HUVEC transplantation group. Transplantation of HUVEC spheroids also resulted in enhanced and prolonged secretion of paracrine factors as well as enhanced expression of factors involved in the recruitment of circulating angiogenic progenitor cells. In summary, transplantation of HUVECs as spheroids enhanced cell survival, increased paracrine factor secretion, and showed a potential as a therapeutic method to treat ischemic tissue damages by promoting angiogenesis.

Original languageEnglish
Pages (from-to)310-319
Number of pages10
JournalTissue Engineering - Part A
Issue number3-4
Publication statusPublished - 2012 Feb 1

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering


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