Human embryonic stem cell-derived vascular progenitor cells capable of endothelial and smooth muscle cell function.
Human embryonic stem cell-derived vascular progenitor cells capable of endothelial and smooth muscle cell function.
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DOI：
10.1016/j.exphem.2010.01.001
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发表时间：
2010-03
影响因子：
2.6
通讯作者：
Kaufman, Dan S.
中科院分区：
文献类型：
--
作者：
Hill, Katherine L.;Obrtlikova, Petra;Alvarez, Diego F.;King, Judy A.;Keirstead, Susan A.;Allred, Jeremy R.;Kaufman, Dan S.
以往的研究表明，内皮细胞(ECs)和平滑肌细胞(SMCs)是由人类胚胎干细胞(HESCs)分化而来的独立细胞系。我们证明了从分化的hESCs中分离出来的CD34+细胞是能够同时产生ECs和SMC的血管前体细胞。这些研究更好地定义了发育起源，揭示了这两种细胞类型之间的关系，并提供了更完整的生物学特征。人胚胎干细胞与M2-10B4基质细胞或表达M2-10B4的WNT1共培养13-15天，形成CD34+细胞群。使用磁性抗体分离试剂盒分离这些细胞，并将其培养在EC培养液中的纤维连接蛋白包被的培养皿中。为了诱导SMC分化，更换培养基并在24-48小时内发生形态和表型变化。CD34+血管前体细胞可分化为ECs和SMC。这两个群体表达各自的细胞特异性转录物和蛋白质，显示细胞内钙离子对各种激动剂的响应，并在与Matrigel共同培养时形成坚固的管状结构。在SMC条件下培养的人脐静脉内皮细胞(HUVEC)不表现出表型或基因的变化。WNT1过表达的基质细胞产生了更多的祖细胞。从单个血管前体细胞群中产生大量内皮细胞和平滑肌细胞的能力有望用于治疗各种疾病和缺血性疾病。这里概述的分步分化方法是一种有效的、可重复性的方法，具有适合临床应用的大规模培养的潜力。
Previous studies have demonstrated development of endothelial cells (ECs) and smooth muscle cells (SMCs) as separate cell lineages derived from human embryonic stem cells (hESCs). We demonstrate CD34+ cells isolated from differentiated hESCs function as vascular progenitor cells capable of producing both ECs and SMCs. These studies better define the developmental origin and reveal the relationship between these two cell types, as well as provide a more complete biological characterization. hESCs are co-cultured on M2-10B4 stromal cells or Wnt1 expressing M2-10B4 for 13–15 days to generate a CD34+ cell population. These cells are isolated using a magnetic antibody separation kit and cultured on fibronectin coated dishes in EC medium. To induce SMC differentiation, culture medium is changed and a morphological and phenotypic change occurs within 24–48 hours. CD34+ vascular progenitor cells give rise to ECs and SMCs. The two populations express respective cell specific transcripts and proteins, exhibit intracellular calcium in response to various agonists, and form robust tube-like structures when co-cultured in Matrigel. Human umbilical vein endothelial cells (HUVEC) cultured under SMC conditions do not exhibit a change in phenotype or genotype. Wnt1 overexpressing stromal cells produced an increased number of progenitor cells. The ability to generate large numbers of ECs and SMCs from a single vascular progenitor cell population is promising for therapeutic use to treat a variety of diseased and ischemic conditions. The step-wise differentiation outlined here is an efficient, reproducible method with potential for large scale cultures suitable for clinical applications.
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骨髓来源的多能细胞是有助于血管化的周细胞
影响因子：
4.8
作者：
Cai, Xiaoxiao;Lin, Yunfeng;Grottkau, Brian E.
通讯作者：
Grottkau, Brian E.
影响因子：
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作者：
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Zago, Marco A.
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作者：
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Gepstein, Lior
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作者：
Ema, M;Faloon, P;Rossant, J
通讯作者：
Rossant, J
影响因子：
20.3
作者：
FENNIE, C;CHENG, J;LASKY, LA
通讯作者：
LASKY, LA