Cord blood stem cell expansion is permissive to epigenetic regulation and environmental cues.
Cord blood stem cell expansion is permissive to epigenetic regulation and environmental cues.
复制标题
DOI：
10.1016/j.exphem.2009.05.012
复制
发表时间：
2009-09
影响因子：
2.6
通讯作者：
Mahmud N
中科院分区：
文献类型：
--
作者：
Araki H;Baluchamy S;Yoshinaga K;Petro B;Petiwala S;Parajuli R;Milhem M;Lavelle D;DeSimone J;Mahmud N
在将其视为成人患者造血重建的替代移植物之前，需要增加一个单位中存在的脐带血（CB）造血干细胞（HSC）的数量。为了进一步优化增加 HSC 数量的策略，我们检查了表观遗传机制介导的 HSC 扩张是否仍然允许外部环境线索。染色质修饰剂 5-aza-2'-脱氧胞苷 (5azaD) 和曲古抑菌素 A (TSA) 通过添加各种细胞因子来改善离体培养过程中 CB 细胞的表观遗传改变。培养后，测定CD34+CD90+细胞数量、其分裂历史、体外克隆形成潜力以及体内造血重建潜力和频率。 5azaD/TSA 处理的 CD34+CD90+ 细胞在扩增程度、克隆形成潜力、细胞分裂率和培养中使用的细胞因子组合的可移植性方面受到很大影响。此外，我们目前的结果证实，依次添加 5azaD 和 TSA 对于 HSC 的扩增至关重要。我们证明，5azaD/TSA 处理后，CD34+CD90+ 细胞分裂的速率也取决于细胞因子混合物，并且这与功能变化相关，包括体外克隆形成潜力和体内重建潜力的改变。我们的研究表明，受表观遗传机制影响的内在因素与外部环境信号在 HSC 扩张的调节中存在相互作用。环境因素可能会加剧表观遗传对 HSC 的影响。分裂速率的调节可能是离体扩增过程中维持 HSC 功能效力的关键决定因素。
Augmentation of the number of cord blood (CB) hematopoietic stem cells (HSC) present in a unit is required before it can be considered as an alternative graft for hematopoietic reconstitution for adult patients. In order to further optimize strategies to augment HSC numbers, we examined whether expansion of HSC mediated by epigenetic mechanisms remains permissive to external environmental cues. The chromatin-modifying agents 5-aza-2′-deoxycytidine (5azaD) and trichostatin A (TSA) were used to ameliorate epigenetic alteration of CB cells during ex vivo culture by adding various cytokines. After culture, CD34+CD90+ cell numbers, their division history, in vitro clonogenic potential, and in vivo hematopoietic reconstitution potential and frequency were determined. 5azaD/TSA-treated, CD34+CD90+ cells were greatly influenced in terms of their degree of expansion, clonogenic potential, cell-division rate, and transplantability by the combination of cytokines used in culture. Furthermore, our current results verify that the sequential addition of 5azaD followed by TSA is crucial for expansion of HSC. We demonstrate that following 5azaD/TSA treatment, the rate of CD34+CD90+ cell division is also dependent on the cytokine cocktail and that this is associated with functional changes, including alteration of in vitro clonogenic potential and in vivo reconstitution potential. Our studies indicate there are interactions between intrinsic factors influenced by epigenetic mechanisms and external environmental signals in the regulation of HSC expansion. Epigenetic influences on HSC can be accentuated by environmental factors. Regulation of the rate of divisions may be a critical determinant for the maintenance of HSC functional potency during ex vivo expansion.
登录
查看更多内容
影响因子：
20.3
作者：
DERCKSEN, MW;GERRITSEN, WR;VANDERSCHOOT, CE
通讯作者：
VANDERSCHOOT, CE
DOI：
10.3324/haematol.13206
发表时间：
2009-02-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Foguenne, Jacques;Di Stefano, Ivano;Gothot, Andre
通讯作者：
Gothot, Andre
影响因子：
30.8
作者：
Cameron, EE;Bachman, KE;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
56.9
作者：
Cheng, T;Rodrigues, N;Scadden, DT
通讯作者：
Scadden, DT
影响因子：
3.6
作者：
Momparler, RL
通讯作者：
Momparler, RL