Nonbone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia
Nonbone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia
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DOI：
10.1161/01.res.0000259562.63718.35
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发表时间：
2007-03-02
影响因子：
20.1
通讯作者：
Heeschen, Christopher
中科院分区：
文献类型：
--
作者：
Aicher, Alexandra;Rentsch, Markus;Heeschen, Christopher
循环祖细胞归巢到出生后新生血管形成的部位并分化成内皮细胞，但关于这些细胞的来源仍存在问题。事实上，最近的一项研究表明，在移植动脉硬化的情况下，非骨髓来源的细胞可能比骨髓来源的细胞更重要。因此，我们的目的是彻底调查的贡献，非骨髓来源的祖细胞的新生血管。我们专门确定了非骨髓来源的祖细胞结合联体模型与反向骨髓移植后，后肢缺血。在该模型中，非骨髓来源的循环祖细胞占纳入缺血后肢的循环祖细胞的74 +/- 13%。越来越多的证据表明，器官，如小肠和肝脏含有相当数量的组织驻留祖细胞，因此，代表了非骨髓来源的祖细胞的推定来源。为了追踪器官来源的祖细胞，我们将性别不匹配的小肠或肝脏分别移植到大鼠体内，然后诱导后肢缺血。这些实验表明，器官来源的祖细胞有助于出生后血管发生（肠：4.7 +/- 3.7%;肝脏：6.3 +/- 2.2%）。基于随后的观察，肝源性非造血c-kit（+）CD 45（-）祖细胞动员诱导后肢缺血，我们前瞻性地分离和静脉输注这些祖细胞从小鼠肝脏。分离的细胞表现出显著的增强新生血管形成和恢复缺血后肢血流的能力（无细胞：正常血流的26.4 +/-4.8%; c-kit（+）CD 45（-）细胞：正常血流的67.0 +/-8.0%; P < 0.01）。总之，我们发现非骨髓来源的c-kit（+）CD 45（-）祖细胞对出生后新生血管形成的贡献程度与骨髓来源的祖细胞相似。肠道和肝脏是动员的组织驻留祖细胞的丰富来源。
Circulating progenitor cells home to sites of postnatal neovascularization and differentiate into endothelial cells but questions remain regarding the source of these cells. Indeed, a recent study suggests that nonbone marrow-derived cells may be even more important than bone marrow-derived cells in the setting of transplant arteriosclerosis. Thus, we aimed to thoroughly investigate the contribution of nonbone marrow-derived progenitor cells for neovascularization. We exclusively identified nonbone marrow-derived progenitor cells by combining a parabiosis model with reverse bone marrow transplantation followed by hindlimb ischemia. In this model, nonbone marrow-derived circulating progenitor cells attributed for 74 +/- 13% of the circulating progenitor cells that incorporated into the ischemic hindlimb. Increasing evidence suggests that organs such as small intestine and liver contain a considerable number of tissue resident progenitor cells and, thus, represent putative sources for nonbone marrow-derived progenitors. To track organ-derived progenitors, we transplanted sex-mismatched small intestine or liver, respectively, into rats followed by induction of hindlimb ischemia. These experiments show that organ-derived progenitor cells are contributing to postnatal vasculogenesis (intestine: 4.7 +/- 3.7%; liver: 6.3 +/- 2.2%). Based on the subsequent observation that liver-derived nonhematopoietic c-kit(+)CD45(-) progenitors are mobilized on induction of hindlimb ischemia, we prospectively isolated and intravenously infused these progenitors from murine livers. The isolated cells demonstrated a marked capacity for enhancing neovascularization and restoring blood flow to the ischemic hindlimb (no cells: 26.4 +/- 4.8% of normal blood flow; c-kit(+)CD45(-)cells: 67.0 +/- 8.0% of normal flow; P < 0.01). In conclusion, we find that nonbone marrow-derived c-kit(+)CD45(-) progenitors contribute to postnatal neovascularization to an extent that is similar to that of bone marrow-derived progenitor cells. Intestine and liver represent a rich source for mobilized tissue-residing progenitor cells.