IDEAS 2.0 Centre of Innovation, VA Salt Lake City Health Care System, Salt Lake City, UT, USA.
Division of Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
Microcirculation. 2020 Oct;27(7):e12646. doi: 10.1111/micc.12646. Epub 2020 Aug 28.
It is not known how activation of the hypoxia-inducible factor (HIF) pathway in pericytes, cells of the microvascular wall, influences new capillary growth. We tested the hypothesis that HIF-activated pericytes promote angiogenesis in a neonatal model of spinal cord injury (SCI).
Human placental pericytes stimulated with cobalt chloride and naïve pericytes were injected into the site of a thoracic hemi-section of the spinal cord in rat pups on postnatal day three (P3). Hindlimb motor recovery and Doppler blood flow perfusion at the site of transection were measured on P10. Immunohistochemistry was used to visualize vessel and neurofilament density for quantification.
Injection of HIF-activated pericytes resulted in greater vascular density in males but did not result in improved motor function for males or females. Injection of non-HIF-activated pericytes resulted improved motor function recovery in both sexes (males, 2.722 ± 0.31-fold score improvement; females, 3.824 ± 0.58-fold score improvement, P < .05) but produced no significant changes in vessel density.
HIF-activated pericytes promote vascular density in males post-SCI. Acute delivery of non-HIF-activated pericytes at the site of injury can improve motor recovery post-SCI.
尚不清楚血管周细胞（微血管壁细胞）中缺氧诱导因子（HIF）通路的激活如何影响新毛细血管的生长。我们检验了这样一个假设，即 HIF 激活的血管周细胞可促进脊髓损伤（SCI）新生动物模型中的血管生成。
在新生大鼠（出生后第 3 天，P3）的胸段半切脊髓部位注射用氯化钴和幼稚周细胞刺激的人胎盘周细胞。在 P10 时测量断端部位的后肢运动恢复和多普勒血流灌注。使用免疫组织化学方法可视化血管和神经丝密度以进行定量分析。
HIF 激活的周细胞注射导致雄性动物的血管密度增加，但并未改善雄性或雌性动物的运动功能。非 HIF 激活的周细胞注射可改善两性动物的运动功能恢复（雄性动物，2.722 ± 0.31 倍评分改善；雌性动物，3.824 ± 0.58 倍评分改善，P <.05），但对血管密度没有显著影响。
HIF 激活的周细胞可促进 SCI 后雄性动物的血管密度增加。损伤部位急性递送非 HIF 激活的周细胞可改善 SCI 后的运动恢复。
