Taura Daisuke, Sone Masakatsu, Homma Koichiro, Oyamada Naofumi, Takahashi Kazutoshi, Tamura Naohisa, Yamanaka Shinya, Nakao Kazuwa
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Arterioscler Thromb Vasc Biol. 2009 Jul;29(7):1100-3. doi: 10.1161/ATVBAHA.108.182162. Epub 2009 May 7.
Induced pluripotent stem (iPS) cells are a novel stem cell population derived from human adult somatic cells through reprogramming using a defined set of transcription factors. Our aim was to determine the features of the directed differentiation of human iPS cells into vascular endothelial cells (ECs) and mural cells (MCs), and to compare that process with human embryonic stem (hES) cells.
We previously established a system for differentiating hES cells into vascular cells. We applied this system to human iPS cells and examined their directed differentiation. After differentiation, TRA1-60(-) Flk1(+) cells emerged and divided into VE-cadherin-positive and -negative populations. The former were also positive for CD34, CD31, and eNOS and were consistent with ECs. The latter differentiated into MCs, which expressed smooth muscle alpha-actin and calponin after further differentiation. The efficiency of the differentiation was comparable to that of human ES cells.
We succeeded in inducing and isolating human vascular cells from iPS cells and indicate that the properties of human iPS cell differentiation into vascular cells are nearly identical to those of hES cells. This work will contribute to our understanding of human vascular differentiation/development and to the development of vascular regenerative medicine.
诱导多能干细胞(iPS细胞)是通过使用一组特定的转录因子进行重编程,从人类成体细胞中获得的新型干细胞群体。我们的目的是确定人类iPS细胞定向分化为血管内皮细胞(ECs)和平滑肌细胞(MCs)的特征,并将该过程与人类胚胎干细胞(hES细胞)进行比较。
我们之前建立了一个将hES细胞分化为血管细胞的系统。我们将该系统应用于人类iPS细胞,并检测它们的定向分化。分化后,出现了TRA1-60(-) Flk1(+)细胞,并分为VE-钙黏蛋白阳性和阴性群体。前者对CD34、CD31和eNOS也呈阳性,与ECs一致。后者分化为MCs,进一步分化后表达平滑肌α-肌动蛋白和钙调蛋白。分化效率与人类ES细胞相当。
我们成功地从iPS细胞中诱导并分离出人类血管细胞,并表明人类iPS细胞分化为血管细胞的特性与hES细胞几乎相同。这项工作将有助于我们对人类血管分化/发育的理解以及血管再生医学的发展。