GENERATION OF NK CELLS FROM CD34+ HEMATOPOIETIC STEM CELLS

由 CD34 造血干细胞产生 NK 细胞

• 批准号: 04671508
• 负责人: NAKAUCHI Hiromitsu
• 金额: $ 1.34万
• 依托单位: THE INSTITUTE OF PFYSICAL AND CHEMICAL RESEARCH (1993)University of Tsukuba (1992)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671508/
• 关键词: Hematopoietic stem cells; NK cells; Stem Cell Factor; IL-2; IL-3; stroma cells; CD34; CD33; ストローマ細胞; NK前駆細胞; stem cell factor

NK cells are believed to play a role in the primary host defense against tumor cells and virus-infected cells. Although it is known that NK precursor cells reside in the bone marrow (BM), the developmental sequence and molecular mechanisms associated with their differentiation into NK cells remain controversial. In order to clarify the lineage relationship between NK cells and other hematolymphoid cells, a cell culture system was established for human CD34^+ hematopoietic stem cells(HPSC). In medium containing both IL-2 and stem cell factor (SCF), NK cells differentiated from FACS-sorted CD34^+ HPSC, and when CD34^+ HPSC were fractionated according to CD33 expression, NK cells were obtained only from CD34^+CD33^+ cells. By contrast, CD34^+CD33^- cells grown in medium supplemented with IL-3 and SCF for 7 days before exposure to IL-2 also differentiated into NK cells after an additional 21 days of culture. These data provide direct evidence that NK cells arise from HPSC and reveal the identity of the cytokines required for their differentiation.

据信NK细胞在针对肿瘤细胞和病毒感染细胞的主要宿主防御中起作用。尽管众所周知，NK前体细胞驻留在骨髓（BM）中，但与分化为NK细胞相关的发育序列和分子机制仍然存在争议。为了阐明NK细胞与其他血小结构细胞之间的谱系关系，为人CD34^+造血干细胞（HPSC）建立了细胞培养系统。在包含IL-2和干细胞因子（SCF）的培养基中，NK细胞与FACS分类的CD34^+ HPSC区分开，当CD34^+ HPSC根据CD33表达分馏时，仅在CD34^+ CD33中获得NK细胞。 ^+细胞。相比之下，在培养21天后，在暴露于IL-2的培养基中生长的CD34^+CD33^ - 在补充IL-3和SCF的培养基中生长了7天，也分化为NK细胞。这些数据提供了直接证据，表明NK细胞由HPSC产生，并揭示了其分化所需的细胞因子的身份。

项目成果

Akira Shibuya, Hiroshi Kojima, Kazuko Shibuya, Kazunari Nagayoshi, Toshio Nagasawa and Hiromitsu Nakauchi: "Enrichment of Interleukin-2-responsive Natural Killer progenitors in human bone marrow." Blood. 81. 1819-1826 (1993)

Akira Shibuya、Hiroshi Kojima、Kazuko Shibuya、Kazunari Nagayoshi、Toshio Nagasawa 和 Hiromitsu Nakauchi：“人类骨髓中白细胞介素 2 反应性自然杀伤祖细胞的富集。”

Yukio Nakamura,et.al.: "Two altemative forms of cDNA encoding CD34." Exp.Hematology.21. 236-242 (1993)

Yukio Nakamura 等人：“编码 CD34 的 cDNA 的两种替代形式。”

Yukio Nakamura, Hajime Komano and Hiromitsu Nakauchi: "Two alternative forms of cDNA encoding CD34" Exp.Hematology. 21. 236-242 (1993)

Yukio Nakamura、Hajime Komano 和 Hiromitsu Nakauchi：“编码 CD34 的 cDNA 的两种替代形式”Exp.Hematology。

Yuji Gunji, Mitsuru Nakamura, Toshihiko, Hagiwara, Kayoko, Hayakawa, Hirohisa Matsushita, Hisao Osawa, Kazunari Nagayoshi, Hiromitsu Nakauchi, Masayoshi Yanagisawa, Yasusada Miura, and Toshio Suda: "Expression and function of adhension molecules on human

Yuji Gunji、Mitsuru Nakamura、Toshihiko、Hagiwara、Kayoko、Hayakawa、Hirohisa Matsushita、Hisao Osawa、Kazunari Nagayoshi、Hiromitsu Nakauchi、Masayoshi Yanagisawa、Yasusada Miura 和 Toshio Suda：“粘附分子在人体上的表达和功能

Akira Shibuya: "Enrichment of Interleukin-2-responsive natural killer progenitors in human bone marrow." Blood.

Akira Shibuya：“人类骨髓中白细胞介素 2 反应性自然杀伤祖细胞的富集。”