キタハラ　シユウジ   Kitahara Shiyuuji   北原　秀治    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   特任准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Endothelial cell transplantation in tumors restores normal vasculature, reduces tumor hypoxia, and suppresses tumor outgrowth.
掲載誌名	正式名：Journal of oral biosciences 略　 称：J Oral Biosci ISSNコード：18803865/13490079
掲載区分	国外
巻・号・頁	58(4),pp.150-157
著者・共著者	Kitahara Shuji, Matsui Aya, Yoshii Asuka, Kuwahara Yoshikazu, Nishio Miwako, Saeki Kumiko, Ezaki Taichi
発行年月	2016/11
概要	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