血小板の産生機序は不明点が多い。本研究は, 脂肪幹細胞から分化し, 自らトロンボポエチンを分泌・消費しながら高率に巨核球分化に向かうプレ巨核球前駆細胞の同定を目的とした。候補解析を基にFACSで得たCD71の発現の有無の細胞を巨核球分化誘導培地で培養した。その巨核球産生量はCD71陰性脂肪幹細胞に比し, 約6倍の産生を認めた。single cellの遺伝子解析結果との抱き合わせ解析によりc-MPLに着目した検討を行った結果, c-MPL陽性脂肪幹細胞では高い頻度の巨核球産生・血小板産生を認めた。本研究は, CD71/c-MPL陽性脂肪幹細胞は高率に巨核球に分化する細胞であることを示した。
Megakaryocytes (MKs) and platelet production are complex processes beginning with stem cells. We recently reported that adipose-derived stem/stromal cells (ASCs) differentiate into MKs and platelets. Although ASCs are not hematopoietic lineage cells, the differentiation of ASCs into MKs does not require gene transfer as they utilize endogenous genes and is dependent on endogenous thrombopoietin (TPO). ASCs have various types of cells. Thus, this study aimed to identify pre megakaryocytic progenitor cells, MK-biased cells in ASCs. We performed flowcytometry analysis, FACS, and single cell analysis (gene expression), and the data suggested that MK and platelet production from CD71- and/or c-MPL-expressing ASCs was higher than that CD71/c-MPL-negative ASCs. We also showed that the production of endogenous TPO via the transferrin receptor CD71 is involved in MK differentiation from ASCs. Taken together, CD71- and/or c-MPL-expressing ASCs are involved in MK-biased cells in ASCs.

研究種目 : 基盤研究(C)(一般)
研究期間 : 2014～2016
課題番号 : 26461410
研究分野 : 血栓止血学, 血液学