Proangiogenic features of Wharton's jelly-derived mesenchymal stromal/stem cells and their ability to form functional vessels
Proangiogenic features of Wharton's jelly-derived mesenchymal stromal/stem cells and their ability to form functional vessels
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DOI：
10.1016/j.biocel.2012.12.001
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发表时间：
2013-03-01
影响因子：
4
通讯作者：
Joe, Young Ae
中科院分区：
文献类型：
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作者：
Choi, Moran;Lee, Hyun-Sun;Joe, Young Ae
来源于人Wharton‘s Jelly的间充质基质/干细胞(WJ-MSC)已成为自体和同种异体细胞治疗的良好来源。在这里，我们表征了WJ-MSCs的前血管生成特征，并在体内模型中检测了它们形成功能性血管的能力。首先，我们检测了WJ-MSCs在内皮细胞生长培养液中培养后是否表达内皮细胞和平滑肌细胞特异性标志物。WJ-MSCs在mRNA和蛋白水平表达血管内皮细胞特异性标志物VEGFR1，但不表达其他特异性标志物(VEGFR2、Tie2、vWF、CD31和VE-cadherin)。相反，WJ-MSCs表达平滑肌细胞特异性标志物α-SMA、PDGFR-β和Calponin，不能在Matrigel上形成管状结构和管腔。WJ-MSCs分泌血管生成素、IGFBP-3、MCP-1和IL-8等生长因子，刺激内皮细胞增殖、迁移和管状形成。将悬浮在Matrigel中的WJ-MSCs移植到裸鼠体内，7d后可形成含有红细胞的功能性血管。然而，种植内皮细胞悬浮的Matrigel导致没有血管灌流。移植的WJ-MSCs的钙蛋白或PDGFR-β染色呈阳性，并与标记的BS-凝集素B4染色的小鼠内皮细胞的衬里相邻。在小鼠后肢缺血模型中，与对照组相比，骨髓间充质干细胞(5×10(5)细胞)移植到缺血肢体可以改善肢体的血流灌注恢复和新生血管。结果提示，WJ-MSCs通过分泌旁分泌因子和作为血管周围前体细胞促进新生血管形成和灌流，可有效地用于缺血性疾病的细胞治疗。(C)2012爱思唯尔有限公司。保留所有权利。
Mesenchymal stromal/stem cells derived from human Wharton's jelly (WJ-MSC) have emerged as a favorable source for autologous and allogenic cell therapy. Here, we characterized the proangiogenic features of WJ-MSCs and examined their ability to form functional vessels in in vivo models. First, we examined whether WJ-MSCs express endothelial and smooth muscle cell specific markers after culture in endothelial growth media. WJ-MSCs expressed an endothelial specific marker, VEGFR1, at mRNA and protein levels, but did not express other specific markers (VEGFR2, Tie2, vWF, CD31, and VE-cadherin). Rather, WJ-MSCs expressed smooth muscle cell specific markers, alpha-SMA, PDGFR-beta and calponin, and were unable to form tube-like structures with lumen on Matrigel. WJ-MSCs secreted growth factors including angiogenin, IGFBP-3, MCP-1, and IL-8, which stimulated endothelial proliferation, migration, and tube formation. When WJ-MSCs suspended in Matrigel were implanted into nude mice, it led to formation of functional vessels containing erythrocytes after 7 days. However, implantation of endothelial cell-suspended Matrigel resulted in no perfused vessels. The implanted WJ-MSCs were stained positively for calponin or PDGFR-beta and were located adjacent to the lining of mouse endothelial cells that were stained with labeled BS-lectin B4. In a murine hindlimb ischemia model, the transplantation of MSCs (5 x 10(5) cells) into the ischemic limbs improved perfusion recovery and neovascularization of the limbs compared to control group. Therefore, the results suggest that WJ-MSCs promote neovascularization and perfusion by secreting paracrine factors and by functioning as perivascular precursor cells, and that WJ-MSCs can be used efficiently for cell therapy of ischemic disease. (c) 2012 Elsevier Ltd. All rights reserved.