Potential Variables for Improved Reproducibility of Neuronal Cell Grafts at Stroke Sites.

Potential Variables for Improved Reproducibility of Neuronal Cell Grafts at Stroke Sites.
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DOI:
10.3390/cells11101656
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发表时间:
2022-05-17
期刊:
影响因子:
6
通讯作者:
Hebert, Jean M.
Hebert, Jean M.
中科院分区:
生物学2区
文献类型:
--
作者:
Krzyspiak, Joanna;Khodakhah, Kamran;Hebert, Jean M.

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人们对使用细胞替代物修复缺血性中风造成的损伤越来越感兴趣。然而,细胞移植的有用性可能受到其成功植入中观察到的变异性的限制。例如,我们最近表明,尽管在小鼠中风部位形成大移植物(高达15 mm3)需要包含供体来源的血管细胞,但移植物的整体大小仍然高度可变。这种变异性可能是由于用于移植的细胞或宿主环境的差异。在这里,作为可能影响植入的因素,我们测试宿主性别,宿主年龄,缺血损伤的程度,缺血后移植的时间,供体细胞成熟度的微小差异,以及移植时的细胞活力。我们发现中风部位的移植物大小与缺血性损伤的大小、宿主性别(具有与损伤相关的移植物大小的女性)、供体细胞成熟度和宿主年龄相关,但与中风后移植的时间无关。一个通用的线性模型显示,移植物的大小是最好的预测中风的严重程度结合供体细胞的成熟度。这些发现可以作为提高基于细胞的修复疗法的可重复性的指导。
Interest is growing in using cell replacements to repair the damage caused by an ischemic stroke. Yet, the usefulness of cell transplants can be limited by the variability observed in their successful engraftment. For example, we recently showed that, although the inclusion of donor-derived vascular cells was necessary for the formation of large grafts (up to 15 mm3) at stroke sites in mice, the size of the grafts overall remained highly variable. Such variability can be due to differences in the cells used for transplantation or the host environment. Here, as possible factors affecting engraftment, we test host sex, host age, the extent of ischemic damage, time of transplant after ischemia, minor differences in donor cell maturity, and cell viability at the time of transplantation. We find that graft size at stroke sites correlates with the size of ischemic damage, host sex (females having graft sizes that correlate with damage), donor cell maturity, and host age, but not with the time of transplant after stroke. A general linear model revealed that graft size is best predicted by stroke severity combined with donor cell maturity. These findings can serve as a guide to improving the reproducibility of cell-based repair therapies.
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