Angiogenesis in Liquid Tumors: An In Vitro Assay for Leukemic-Cell-Induced Bone Marrow Angiogenesis

Yi Zheng, Yubing Sun, Xinwei Yu, Yue Shao, Ping Zhang, Guohao Dai, Jianping Fu

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

The critical role of angiogenesis for solid tumor growth and metastatic spread has been well established. In contrast, even though increased vascularity has been commonly observed in bone marrows of patients with hematological malignancies (liquid tumors), the pathophysiology of leukemia-induced angiogenesis in the bone marrow remains elusive. This paper demonstrates the usage of a microengineered 3D biomimetic model to study leukemic-cell-induced bone marrow angiogenesis. Rational design of the 3D angiogenesis chip incorporating endothelial cells (ECs), leukemic cells, and bone marrow stromal fibroblasts provide an efficient biomimetic means to promote and visualize early angiogenic processes. Morphological features of angiogenesis induced by three different leukemic cell lines (U937, HL60, and K562) are investigated and compared. Quantitative measurements of angiogenic factors secreted from monocultures and cocultures of leukemic cells with bone marrow stromal fibroblasts suggest a synergistic relationship between ECs, leukemic cells, and bone marrow stromal fibroblasts for angiogenic induction, and also confirm the necessity of conducting functional angiogenic assays in proper 3D biomimetic cell culture systems like the one developed in this work.

Original languageEnglish (US)
Pages (from-to)1014-1024
Number of pages11
JournalAdvanced Healthcare Materials
Volume5
Issue number9
DOIs
StatePublished - May 11 2016
Externally publishedYes

Keywords

  • Angiogenesis
  • Bone marrow microenvironment
  • Leukemia
  • Microfluidics
  • Organs-on-chips

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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