Type-2 pericytes participate in normal and tumoral angiogenesis
Type-2 pericytes participate in normal and tumoral angiogenesis
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DOI：
10.1152/ajpcell.00084.2014
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发表时间：
2014-07-01
影响因子：
5.5
通讯作者：
Delbono, Osvaldo
中科院分区：
文献类型：
--
作者：
Birbrair, Alexander;Zhang, Tan;Delbono, Osvaldo
组织的生长和功能依赖于血管化，血管不足或过多会加剧许多人类疾病。参与血管生成的生物学过程的鉴定将决定调节减少或过度血管形成的策略。我们研究周细胞的重要作用。它们的异质形态，分布，起源和生理已被描述。使用双转基因Nestin-GFP/NG 2-DsRed小鼠，我们鉴定了两个周细胞亚群。我们发现Nestin-GFP（-）/NG 2-DsRed（+）（1型）和Nestin-GFP（+）/NG 2-DsRed（+）（2型）周细胞在体内附着在小血管和大血管的壁上;在体外，2型周细胞而不是1型周细胞激发内皮细胞形成新血管。基质胶试验表明，只有2型周细胞参与正常的血管生成。此外，当癌细胞被移植到Nestin-GFP/NG 2-DsRed小鼠中时，1型周细胞没有穿透肿瘤，而2型周细胞在其血管生成期间被招募。由于抑制血管生成是癌症治疗中有前途的策略，2型周细胞可以提供对治疗恶性肿瘤中的信号传导和药理学操纵敏感的细胞靶点。这项工作还报告了2型周细胞改善缺血性后肢血液灌注的潜力，表明其治疗缺血性疾病的潜力。
Tissue growth and function depend on vascularization, and vascular insufficiency or excess exacerbates many human diseases. Identification of the biological processes involved in angiogenesis will dictate strategies to modulate reduced or excessive vessel formation. We examine the essential role of pericytes. Their heterogeneous morphology, distribution, origins, and physiology have been described. Using double-transgenic Nestin-GFP/NG2-DsRed mice, we identified two pericyte subsets. We found that Nestin-GFP(-)/NG2-DsRed(+) (type-1) and Nestin-GFP(+)/NG2-DsRed(+) (type-2) pericytes attach to the walls of small and large blood vessels in vivo; in vitro, type-2, but not type-1, pericytes spark endothelial cells to form new vessels. Matrigel assay showed that only type-2 pericytes participate in normal angiogenesis. Moreover, when cancer cells were transplanted into Nestin-GFP/NG2-DsRed mice, type-1 pericytes did not penetrate the tumor, while type-2 pericytes were recruited during its angiogenesis. As inhibition of angiogenesis is a promising strategy in cancer therapy, type-2 pericytes may provide a cellular target susceptible to signaling and pharmacological manipulation in treating malignancy. This work also reports the potential of type-2 pericytes to improve blood perfusion in ischemic hindlimbs, indicating their potential for treating ischemic illnesses.