Isolation of tissue-resident endothelial stem cells and their use in regenerative medicine
Isolation of tissue-resident endothelial stem cells and their use in regenerative medicine
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DOI：
10.1186/s41232-019-0098-9
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发表时间：
2019-05-08
影响因子：
8.1
通讯作者：
Takakura, Nobuyuki
中科院分区：
文献类型：
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作者：
Iba, Tomohiro;Naito, Hisamichi;Takakura, Nobuyuki
工作背景：在新生血管的萌芽过程中，位于尖端细胞后面的柄细胞产生用于新血管伸长的内皮细胞（EC）。我们假设，茎细胞可能具有内皮祖细胞的特性，因为它们的高度增殖能力。我们在后肢肌肉的预先存在的血管的EC中进行了Hoechst染料DNA染色，发现内皮侧群体（E-SP）细胞具有高度的EC产生能力，其具有丰富的ABC转运体快速流出Hoechst。方法：我们研究了E-SP细胞在成年小鼠脂肪组织、皮肤和胎盘中的存在，并分析了E-SP细胞在CD 31（+）CD 45（-）ECs中的增殖能力。结果：E-SP细胞在所有组织中均有表达。然而，通过对OP 9细胞的体外集落形成分析，我们发现来自脂肪组织和皮肤的E-SP细胞具有高度的增殖能力，而来自胎盘的E-SP细胞则没有。结论：脂肪组织和皮肤是获得血管内皮干细胞的有效来源，可用于再生医学血管再生的研究。
Background: During sprouting angiogenesis, stalk cells, localized behind tip cells, generate endothelial cells (ECs) for the elongation of new vessels. We hypothesized that stalk cells may have endothelial progenitor cell properties because of their highly proliferative ability. We conducted Hoechst dye DNA staining in ECs of preexisting blood vessels from hind limb muscle and found that endothelial-side population (E-SP) cells, which efflux Hoechst rapidly with abundant ABC transporters, show highly producing ability of ECs. We previously showed the existence of E-SP cells in hind limb muscle, retina, and liver, but not in other tissues such as adipose tissue, skin, and placenta.Methods: We investigated the existence of E-SP cells and analyzed their proliferative ability among CD31(+)CD45(-) ECs from adipose tissue, skin, and placenta of adult mice. We also analyzed the neovascular formation of E-SP cells from adipose tissue in vivo.Results: We detected E-SP cells in all tissues examined. However, by in vitro colony formation analysis on OP9 cells, we found that E-SP cells from adipose tissue and skin, but not from placenta, have highly proliferative ability. Moreover, E-SP cells from adipose tissue could contribute to the neovascular formation in hind limb ischemia model.Conclusion: The adipose tissue and skin are available sources to obtain endothelial stem cells for conducting therapeutic angiogenesis in regenerative medicine.