Mesenchymal stem cells can participate in ischemic neovascularization.
Mesenchymal stem cells can participate in ischemic neovascularization.
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DOI：
10.1097/prs.0b013e318191be4a
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发表时间：
2009-02
影响因子：
3.6
通讯作者：
Gurtner GC
中科院分区：
文献类型：
--
作者：
Hamou C;Callaghan MJ;Thangarajah H;Chang E;Chang EI;Grogan RH;Paterno J;Vial IN;Jazayeri L;Gurtner GC
骨髓细胞有助于缺血性新生血管形成，但这些细胞的特性仍不明确。作者将间充质干细胞确定为一种源于骨髓的祖细胞群，它能够在缺血反应中植入外周组织。
采用了一种皮肤缺血的小鼠模型。在不同时间点采集骨髓、血液和皮肤，并对间充质和造血标记物进行流式细胞术分析（每个时间点n = 3到7）。利用联体共生模型将供体绿色荧光蛋白（GFP）阳性小鼠与受体野生型小鼠配对，通过荧光显微镜检查祖细胞在缺血组织中的植入情况，并通过流式细胞术分析植入细胞的内皮和间充质标记物。在体外，通过分析（1）间充质干细胞摄取DiI - 乙酰化低密度脂蛋白和Alexa Fluor凝集素的能力，以及（2）与GFP标记的内皮细胞共培养或在缺氧/血管内皮生长因子刺激下间充质干细胞的表型变化，来检测骨髓和脂肪来源的间充质干细胞获得内皮特性的能力。
在体内，骨髓间充质干细胞群在手术后立即显著减少，随后这些细胞植入缺血组织。植入的细胞缺乏全造血抗原CD45，这与间充质来源相符。在体外，骨髓和脂肪来源的间充质干细胞摄取DiI - 乙酰化低密度脂蛋白和Alexa Fluor凝集素，并在缺氧条件下表达内皮标记物。
作者的数据表明间充质前体细胞可产生内皮祖细胞。因此，增加间充质干细胞群的细胞疗法可能是目前缺血性血管疾病疗法的有力替代方案。
Cells from the bone marrow contribute to ischemic neovascularization, but the identity of these cells remains unclear. The authors identify mesenchymal stem cells as a bone marrow–derived progenitor population that is able to engraft into peripheral tissue in response to ischemia. A murine model of skin ischemia was used. Bone marrow, blood, and skin were harvested at different time points and subjected to flow cytometric analysis for mesenchymal and hematopoietic markers (n = 3 to 7 per time point). Using a parabiotic model pairing donor green fluorescent protein (GFP)–positive with recipient wild-type mice, progenitor cell engraftment was examined in ischemic tissue by fluorescence microscopy, and engrafted cells were analyzed by flow cytometry for endothelial and mesenchymal markers. In vitro, the ability of both bone marrow–and adipose-derived mesenchymal stem cells to adopt endothelial characteristics was examined by analyzing (1) the ability of mesenchymal stem cells to take up DiI-acetylated low-density lipoprotein and Alexa Fluor lectin, and (2) phenotypic changes of mesenchymal stem cells co-cultured with GFP-labeled endothelial cells or under hypoxic/vascular endothelial growth factor stimulation. In vivo, the bone marrow mesenchymal stem cell population decreased significantly immediately after surgery, with subsequent engraftment of these cells in ischemic tissue. Engrafted cells lacked the panhematopoietic antigen CD45, consistent with a mesenchymal origin. In vitro, bone marrow–and adipose-derived mesenchymal stem cells took up DiI-acetylated low-density lipoprotein and Alexa Fluor lectin, and expressed endothelial markers under hypoxic conditions. The authors’ data suggest that mesenchymal precursor cells can give rise to endothelial progenitors. Consequently, cell-based therapies augmenting the mesenchymal stem cell population could represent powerful alternatives to current therapies for ischemic vascular disease.