KITAHARA Shuji
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Associate Professor (Fixed Term)
Article types Original article
Language English
Peer review Peer reviewed
Title Endothelial cell transplantation in tumors restores normal vasculature, reduces tumor hypoxia, and suppresses tumor outgrowth.
Journal Formal name：Journal of oral biosciences
Abbreviation：J Oral Biosci
ISSN code：18803865/13490079
Domestic / ForeginForegin
Volume, Issue, Page 58(4),pp.150-157
Author and coauthor Kitahara Shuji, Matsui Aya, Yoshii Asuka, Kuwahara Yoshikazu, Nishio Miwako, Saeki Kumiko, Ezaki Taichi
Publication date 2016/11
Summary OBJECTIVES:Vascular normalization, or restoration of the normal structure and function of blood vessels, using molecular-targeted therapy, has emerged as a potential strategy for treating malignant cancer and other vascular disorders. We hypothesized that restoring tumor blood vessels to their normal state would alleviate hypoxic conditions and potentially enhance the delivery of anticancer drugs. Our objective was to determine if transplanting normal endothelial cells into tumor-bearing mice could trigger vascular normalization.METHODS:Tumor cells were injected into the dorsal subcutis of severe combined immunodeficiency (SCID) mice (day 0). Tumor-bearing mice were injected intraperitoneally with cisplatin at day 14 to create scaffolds for blood vessel formation in the tumors. At day 28, human microvascular endothelial cells (HMVECs) or human embryonic stem-derived endothelial cells (ESECs) were transplanted into the necrotic regions of the tumor to induce normal angiogenesis.RESULTS:Microscopic observation revealed that the transplanted HMVECs or ESECs formed anastomoses with the host mouse vasculature. In addition, blood vessels with blood flow could be detected after 14d. Blood vessels reconstituted by HMVECs or ESECs exhibited normal vasculature, and tumor growth was significantly inhibited upon treatment.CONCLUSION:Reconstruction of tumor blood vessels to their normal state alleviated hypoxic conditions and improved the efficiency of drug delivery; the present approach provides a useful model for the development of new cancer therapies.
DOI 10.1016/j.job.2016.05.003
PMID 32512683