Possible mechanism of hematopietic stem cells homing to the bone marrow microenvironment

造血干细胞归巢骨髓微环境的可能机制

• 批准号: 13671048
• 负责人: MAEKAWA Taira
• 金额: $ 2.3万
• 依托单位: KYOTO UNIVERSITY (2002)The University of Tokyo (2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671048/
• 关键词: cord blood transplantation; hematopietic stem cell; chemokine; homing

We found that the stromal cell derived factor-1/pre-B cell growth stimulating factor (SDF1/PBSF) receptor, CXCR4, is expressed on human CD34^+ bone marrow (BM) cells. Stringently FACS-sorted CD34^+CXCR4^+ BM cells completely lack myeloid, erythroid, megakaryocytic, and mixed colony forming potential (myeloid progenitors), but give rise to B and T lymphoid progenitors, whereas CD34^+CXCR4^- BM cells can generate colonies formed by myeloid progenitors and can also develop into these lymphoid progenitors. Therefore, expression of CXCR4 on CD34^+ BM cells can allow lymphoid progenitors to be discriminated from myeloid progenitors. Since CD34^+CXCR4^+ cells are differentiated from CD34^+CXCR4^- cells, multipotential progenitors located in the BM are likely to be negative for CXCR4 expression. CXCR4 seems to be expressed earlier than the interleukin-7 receptor and terminal deoxynucleotidyl transferase during early lymphohemopoiesis. These results suggest that the expression of CXCR4 on CD34^+ BM cells is one of the phenotypic alterations for committed lymphoid progenitors.

我们发现基质细胞衍生因子-1/前B细胞生长刺激因子（SDF 1/PBSF）受体CXCR 4在人CD 34 ^+骨髓（BM）细胞上表达。经严格FACS分选的CD 34 ^+ CXCR 4 ^+ BM细胞完全缺乏髓系、红系、巨核细胞和混合集落形成能力（髓系祖细胞），但可产生B和T淋巴祖细胞，而CD 34 ^+ CXCR 4 ^- BM细胞可产生髓系祖细胞形成的集落，也可发育成这些淋巴祖细胞。因此，CXCR 4在CD 34 ^+ BM细胞上的表达可以使淋巴样祖细胞与髓样祖细胞区分开来。由于CD 34 ^+ CXCR 4 ^+细胞是从CD 34 ^+ CXCR 4 ^-细胞分化而来的，因此位于骨髓中的多能祖细胞可能不表达CXCR 4。CXCR 4在早期淋巴造血中的表达似乎早于白细胞介素7受体和末端脱氧核苷酸转移酶。这些结果表明，CXCR 4在CD 34 ^+ BM细胞上的表达是定向淋巴祖细胞的表型改变之一。

项目成果

Kuroda, J.et al.: "The third-generation bisphosphonate Zoldronate synergistically augments the anti-Ph+ leukemia"Blood. (印刷中). (2003)

Kuroda, J. 等人：“第三代双膦酸盐 Zoldronate 协同增强抗 Ph+ 白血病”（出版中）。

Ma, R., Wada, M., Yoshino, H., Ebihara, Y., Ishii, T., Manabe, A., Tanaka, R., Maekawa. T., Itoh, M., Mugishima, H., Asano, S., Nakahata, T., Tsuji, K.: "Development of human lymphohematopoietic stem/progenitor cells defined by CD34 and CD81 expressions"B

马，R.，和田，M.，吉野，H.，海老原，Y.，石井，T.，真锅，A.，田中，R.，前川。

Miyamoto, S., Tsuji, K., Maekawa. T., Asano, S., Nakahata, T.: "Inhibitory effect of interleukin-3 on early development of human B-lymphopoi esis"Brit J Haematol. 114(3). 690-697 (2001)

宫本，S.，辻，K.，前川。

Yoshimatsu T et al.: "Prompt and durable hematopoietic reconstitution by unrelated cord blood transplantation in a child with Fanconi anemia"Bone Marrow Transplantation. 27. 767-769 (2001)

Yoshimatsu T 等人：“通过无关的脐带血移植对患有范可尼贫血的儿童进行迅速和持久的造血重建”骨髓移植。

Yoshimasu, T.et al.: "MxA protein expression in patients with virol infection after allogeneic stem cell transplantation"Bone Marrow Transplantation. (印刷中). (2003)

Yoshimasu, T. 等人：“同种异体干细胞移植后病毒感染患者的 MxA 蛋白表达”，骨髓移植（2003 年出版）。