Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
Stem Cell Institute, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
Cells. 2022 May 17;11(10):1656. doi: 10.3390/cells11101656.
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 mm) 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.
人们对利用细胞替代物来修复缺血性中风造成的损伤越来越感兴趣。然而，细胞移植的有效性可能会受到其成功植入的可变性的限制。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 毫米）时需要包含供体来源的血管细胞，但移植物的总体大小仍然高度可变。这种可变性可能是由于用于移植的细胞或宿主环境的差异所致。在这里，我们测试了宿主性别、宿主年龄、缺血损伤的程度、缺血后移植的时间、供体细胞成熟程度的微小差异以及移植时的细胞活力，作为可能影响植入的因素。我们发现，中风部位的移植物大小与缺血损伤的大小、宿主性别（雌性的移植物大小与损伤相关）、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。一般线性模型表明，移植物大小最好由中风严重程度与供体细胞成熟度共同预测。这些发现可以作为提高基于细胞的修复治疗的重现性的指南。
