Identification and isolation of cluster of differentiation (CD) 9-positive pituitary adult stem/progenitor cells in rats

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08475
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Kyorin University
• Principal Investigator: Horiguchi Kotaro 杏林大学, 保健学部, 講師 (10409477)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 下垂体 / 幹細胞 / CD9 / 細胞表面抗原 / 分化 / BMP

Outline of Final Research Achievements

S100β protein, SOX2 and CXCR4-triple positive (S100β/SOX2/CXCR4-positive) cells have been suggested to be adult pituitary stem/progenitor cells. We found that cluster of differentiation (CD) 9 is expressed in the majority of adult rat S100β/SOX2/CXCR4-positive cells, and we succeeded in isolating them using an anti-CD9 antibody with a pluriBead-cascade cell isolation system. Cultivation of these cells showed their capacity to differentiate into endothelial cells via the up-regulation of transcription factor ID2 and bone morphogenetic protein signaling, and horumone-producing cells. By using the anterior lobes of prolactinoma model rats, the localization of S100β/SOX2/CXCR4/CD9-positive cells was confirmed in the tumour-induced neovascularisation region. Thus, the present study should provide a better understanding of the adult tissue stem cells of the anterior lobe and further preclinical and clinical studies on tumour vascularisation.

Free Research Field

組織学

Academic Significance and Societal Importance of the Research Achievements

本研究から、成体下垂体前葉の組織幹細胞と認識されているSOX2陽性細胞で膜タンパク質CD9が発現することが明らかとなり、そのCD9に対する抗体を利用することで、簡便に組織幹細胞を純化することが可能となった。さらに純化した組織幹細胞をin vitroの実験系に供与することで、胚葉を超えた血管内皮細胞への分化に成功した。これは、下垂体前葉の組織幹細胞からの血管新生を伴う組織発生機構の解明と成体でのホルモン産生細胞の供給システム解明への一助となる。さらにプロラクチノーマという下垂体腺腫の発生メカニズム及び薬理学的対処への応用にも寄与すると考える。