Department of Cell Biology, Section Stem Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands.
Exp Hematol. 2010 Nov;38(11):1115-23. doi: 10.1016/j.exphem.2010.07.003. Epub 2010 Jul 17.
Hematopoietic stem cells are key elements for life-long production of mature blood cells. The success of clinical stem cell transplantation may be improved when the number of stem cells that engraft after transplantation can be increased. Here, we investigated in a syngeneic mouse model whether engraftment and reconstitution can be improved by transplantation directly into the bone marrow.
In this study, we directly compared syngeneic transplantation of hematopoietic stem cells into the bone marrow with intravenous administration and assessed reconstitution kinetics and engraftment by bioluminescent imaging and chimerism determination.
Surprisingly, only about 10% of cells injected directly into the femur (intrafemoral, IF) could be retrieved within 5 minutes after injection. Only in the first 48 hours after transplantation, engraftment in IF-transplanted animals was higher compared with intravenous injection. However, at all later time points no differences could be detected using whole body bioluminescence or measuring blood cell reconstitution. Most importantly, we found that IF-transplanted cells did not outcompete cells transplanted intravenously when cotransplanted in the same recipient.
In conclusion, IF transplantation in a murine syngeneic setting revealed no enhanced engraftment. Previous reports on IF transplantation may have relied on escape from immune rejection in xenogeneic or allogeneic models. Therefore, we conclude that stem cells can find the proper microenvironment irrespective of the route of administration.
造血干细胞是终生产生成熟血细胞的关键元素。如果可以增加移植后植入的干细胞数量,临床干细胞移植的成功率可能会提高。在这里,我们在同基因小鼠模型中研究了直接移植到骨髓中是否可以改善植入和重建。
在这项研究中,我们直接比较了将造血干细胞直接移植到骨髓与静脉内给药,并通过生物发光成像和嵌合度测定来评估重建动力学和植入情况。
令人惊讶的是,直接注入股骨(IF)内的细胞中只有约 10%可以在注射后 5 分钟内回收。只有在移植后的前 48 小时,IF 移植动物的植入率高于静脉内注射。然而,在所有后续时间点,使用全身生物发光或测量血细胞重建均未检测到差异。最重要的是,我们发现当在同一受体中共同移植时,IF 移植的细胞并没有与静脉内移植的细胞竞争。
总之,在同种基因小鼠模型中,IF 移植并未显示出增强的植入。先前关于 IF 移植的报告可能依赖于异种或同种异体模型中的免疫逃逸。因此,我们得出结论,干细胞可以找到适当的微环境,而不论给药途径如何。