Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202-5181, United States of America; Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, AMMS, Beijing 100850, China; South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202-5181, United States of America; Zhongshan-Xuhus Hospital and the Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Blood Cells Mol Dis. 2020 Sep;84:102457. doi: 10.1016/j.bcmd.2020.102457. Epub 2020 Jun 1.
Eupalinilide E was assessed for ex-vivo expansion activity on hematopoietic stem cells (HSCs) from human cord blood (CB) CD34 cells in serum-free, SCF, TPO and FL stimulated 7 day cultures. Eupalinilide E ex-vivo enhanced phenotyped (p) HSCs and glycolysis of CD34 cells isolated 7 days after culture as measured by extracellular acidification rate, but did not alone show enhanced NSG engrafting capability of HSCs as determined by chimerism and numbers of SCID Repopulating cells, a quantitative measure of functional human HSCs. This is another example of pHSCs not necessarily recapitulating functional activity of these cells. Lack of effect on engrafting HSCs may be due to a number of possibilities, including down regulation of CXCR4 or of the homing capacity of these treated cells. However, Eupalinilide did act in an additive to synergistic fashion with UM171 to enhance ex vivo expansion of both pHSCs, and functionally engrafting HSCs. While reasons for the disconnect between pHSC and function of HSCs with Eupalinilide E alone cultured CB CD34 cells is yet to be determined, the data suggest possible future use of Eupalinilide and UM171 together to enhance ex vivo production of CB HSCs for clinical hematopoietic cell transplantation.
评估了 eupalinilide E 在无血清、SCF、TPO 和 FL 刺激的 7 天培养物中对来自人脐血 (CB) CD34 细胞的造血干细胞 (HSCs) 的体外扩增活性。Eupalinilide E 在体外增强了表型 (p) HSCs 和 CD34 细胞的糖酵解作用，这是通过细胞外酸化率来衡量的，但单独使用时并未显示出增强 HSCs 在 NSG 中的植入能力，这是通过嵌合和 SCID 重建细胞的数量来衡量的，这是功能性人 HSCs 的定量测量。这是 pHSCs 不一定能再现这些细胞功能活性的另一个例子。对植入 HSCs 没有影响的原因可能有很多，包括 CXCR4 的下调或这些处理细胞的归巢能力。然而，Eupalinilide 确实以增效或协同的方式与 UM171 一起增强了 pHSCs 和功能性植入 HSCs 的体外扩增。虽然单独培养 CB CD34 细胞时，eupalinilide E 与 pHSC 和 HSCs 功能之间的脱节原因尚未确定，但数据表明，未来可能会同时使用 Eupalinilide 和 UM171 来增强 CB HSCs 的体外生产，用于临床造血细胞移植。
