Conversion of vascular endothelial cells into multipotent stem-like cells.
Conversion of vascular endothelial cells into multipotent stem-like cells.
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作者：
间充质干细胞可以产生多种细胞类型，但根据分离方法和组织来源的不同而导致其在临床医学中的用途存在争议。在这里，我们证明血管内皮细胞可以通过 ALK2 受体依赖性机制转化为多能干细胞样细胞。在进行性骨化性纤维发育不良（一种因激活 ALK2 突变而发生异位骨化的疾病）患者或突变 ALK2 转基因小鼠模型的病变中，软骨细胞和成骨细胞表达内皮标记物。 Tie2-Cre 谱系追踪还表明这些细胞的内皮起源。在内皮细胞中表达突变型 ALK2，或使用 ALK2 配体 TGF-β2 或 BMP4 进行处理，可引起内皮-间质转化并获得干细胞样表型。在选择性培养基中，这些细胞分化为成骨细胞、软骨细胞或脂肪细胞。该过程被 ALK2 特异性 siRNA 抑制。内皮细胞向干细胞的转化可能为组织工程提供一种新的方法。
Mesenchymal stem cells can give rise to several cell types, but variations depending on isolation method and tissue source have led to controversies about their usefulness in clinical medicine. Here we show that vascular endothelial cells can transform into multipotent stem-like cells by an ALK2 receptor-dependent mechanism. In lesions from patients with Fibrodysplasia Ossificans Progressiva, a disease where heterotopic ossification occurs as a result of activating ALK2 mutations, or from a mutant ALK2 transgenic mouse model, chondrocytes and osteoblasts express endothelial markers. Tie2-Cre lineage tracing also suggests an endothelial origin of these cells. Expressing mutant ALK2 in endothelial cells, or treatment with the ALK2 ligands TGF-β2 or BMP4, causes endothelial-mesenchymal transition and acquisition of a stem cell-like phenotype. In selective media, these cells differentiate into osteoblasts, chondrocytes, or adipocytes. The process is inhibited by ALK2-specific siRNA. Conversion of endothelial cells to stem-like cells may provide a novel approach to tissue engineering.
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影响因子：
2.5
作者：
Azhar, Mohamad;Runyan, Raymond B.;Gard, Connie;Sanford, L. Philip;Miller, Marian L.;Andringa, Anastasia;Pawlowski, Sharon;Rajan, Sudarsan;Doetschman, Thomas
通讯作者：
Doetschman, Thomas
影响因子：
20.1
作者：
Paruchuri, Sailaja;Yang, Jeong-Hee;Bischoff, Joyce
通讯作者：
Bischoff, Joyce
影响因子：
82.9
作者：
通讯作者：
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影响因子：
2.7
作者：
Boyer, AS;Ayerinskas, II;Runyan, RB
通讯作者：
Runyan, RB
影响因子：
2.7
作者：
Camenisch, TD;Molin, DGM;Klewer, SE
通讯作者：
Klewer, SE