Treatment of Leg Ischemia With Biodegradable Gelatin Hydrogel Microspheres Incorporating Granulocyte Colony-stimulating Factor
Treatment of Leg Ischemia With Biodegradable Gelatin Hydrogel Microspheres Incorporating Granulocyte Colony-stimulating Factor
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DOI：
10.1097/fjc.0b013e31820c9776
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发表时间：
2011-04-01
影响因子：
3
通讯作者：
Minatoguchi, Shinya
中科院分区：
文献类型：
--
作者：
Kawamura, Itta;Takemura, Genzou;Minatoguchi, Shinya
粒细胞集落刺激因子（G-CSF）是一种强有力的血管生成因子。我们假设，G-CSF-浸入明胶水凝胶微球（G-CSF-GHM）注射到缺血腿可能会持续释放少量的G-CSF局部刺激血管生成，而不会产生不利的全身效应。在结扎BALB/c小鼠的右股动脉后，将重组人G-CSF（100 μ g/kg）浸泡的GHM注射到右后肢肌肉中;对照组包括盐水注射组、肌肉内注射G-CSF组、皮下注射G-CSG组和空GHM注射组。8周后，与任何对照组相比，G-CSF-GHM组缺血肢体的血液灌注改善显著增强。尽管G-CSF、外周粒细胞或循环内皮祖细胞的血清浓度没有增加，但该组中不仅毛细血管而且小动脉密度显著增加。接下来，我们在结扎后4周开始用G-CSF-GHM治疗，以检查如果在缺血的慢性阶段进行治疗是否有效。晚期治疗也被发现有效地改善缺血腿的血流量。总之，G-CSF-GHM管理建议是一个有前途的和容易使用的方法来治疗外周动脉疾病，适用于即使在慢性阶段。
Granulocyte colony-stimulating factor (G-CSF) is a potent angiogenic factor. We hypothesized that G-CSF-immersed gelatin hydrogel microspheres (G-CSF-GHMs) injected into the ischemic legs might continuously release a small amount of G-CSF to locally stimulate angiogenesis without unfavorable systemic effects. Just after ligation of the right femoral artery of BALB/c mice, recombinant human G-CSF (100-mu g/kg)-immersed GHM was injected into the right hindlimb muscles; the controls included a saline-injected group, an intramuscularly injected G-CSF group, a subcutaneously injected G-CSG group, and an empty GHM-injected group. Eight weeks later, improvement of blood perfusion to the ischemic limb was significantly augmented in the G-CSF-GHM group compared with any of the control groups. Despite there being no increase in the serum concentration of G-CSF, in peripheral granulocytes, or in circulating endothelial progenitor cells, not only capillary but also arteriolar density was significantly increased in this group. Next, we started treatment with G-CSF-GHM 4 weeks after ligation to examine whether the treatment is effective if performed during the chronic stage of ischemia. The late treatment was also found to effectively improve blood flow in the ischemic leg. In conclusion, G-CSF-GHM administration is suggested to be a promising and readily usable approach to treating peripheral artery disease, applicable even during the chronic stage.