Quesenberry P J, Stewart M F, Peters S, Nillson S, Ramshaw H, Rao S, Tiarks C, Zhong S, Frimberger A, Reilly J
University of Massachusetts Medical Center, Worcester, USA.
Stem Cells. 1997;15 Suppl 1:167-9; discussion 169-70. doi: 10.1002/stem.5530150821.
Hematopoietic stem cell engraftment has traditionally been assessed in irradiated murine hosts. More recently, we and others have shown that engraftment is virtually quantitative in host animals who have received no preconditioning myeloablation. It appears that at the stem cell level, engraftment may even be favored in the normal host. The final phenotypic readout in the engrafted animal is then determined by competition between the engrafted stem cells and the number of residual host stem cells. Further studies have indicated that with cytokine exposure in vitro, in vivo or 5-fluorouracil exposure and consequent stimulation of primitive hematopoietic stem cells to enter cell cycle, an engraftment defect relating to long-term engraftment occurs. This occurs in the face of an expansion of cycling surrogate stem cells as mirrored by the high proliferative potential colony-forming cell. These data indicate that the phenotype of the hematopoietic stem cell, as assessed in vitro, may not give insight into the phenotype of these cells in vivo.
传统上,造血干细胞植入是在经辐照的小鼠宿主体内进行评估的。最近,我们和其他研究人员发现,在未接受预处理骨髓消融的宿主动物中,植入几乎是定量的。似乎在干细胞水平上,正常宿主甚至更有利于植入。植入动物的最终表型读数则由植入的干细胞与残留宿主干细胞数量之间的竞争决定。进一步的研究表明,在体外、体内暴露于细胞因子或暴露于5-氟尿嘧啶并随之刺激原始造血干细胞进入细胞周期后,会出现与长期植入相关的植入缺陷。尽管循环替代干细胞会扩张,如高增殖潜能集落形成细胞所反映的那样,但这种缺陷仍然会出现。这些数据表明,体外评估的造血干细胞表型可能无法洞察这些细胞在体内的表型。