Hypoxia enhances differentiation of hair follicle-associated-pluripotent (HAP) stem cells to cardiac muscle cells
Hypoxia enhances differentiation of hair follicle-associated-pluripotent (HAP) stem cells to cardiac muscle cells
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缺氧增强毛囊相关多能（HAP）干细胞向心肌细胞的分化
DOI：
10.1002/jcb.25734
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发表时间：
2017
影响因子：
4
通讯作者：
and Yasuyuki Amoh
中科院分区：
文献类型：
--
作者：
Kyoumi Shirai;Yuko Hamada;Nobuko Arakawa;Aiko Yamazaki;Natsuko Tohgi;Ryoichi Aki, Sumiyuki Mii;Robert M. Hoffman;and Yasuyuki Amoh
我们先前已经证明，神经干细胞标记物Nestin表达于位于隆起区的毛囊干细胞，被称为毛囊相关多能干细胞(HAP)。小鼠和人的HAP干细胞在体外培养中可以形成角蛋白15阴性、巢蛋白阳性的毛球，在体外可以分化为神经元、胶质细胞、角质形成细胞、平滑肌细胞和黑素细胞。随后，我们证明了表达巢蛋白的干细胞可以影响小鼠模型的神经和脊髓再生。最近，我们证明了HAP干细胞可以分化为跳动的心肌细胞。我们最近观察到，与未添加异丙肾上腺素的HAP干细胞相比，异丙肾上腺素能在培养中引导HAP干细胞大量分化为心肌细胞。加入激活素A、骨形态发生蛋白4和碱性成纤维细胞生长因子，以及异丙肾上腺素，可以诱导心肌细胞形成跳动的心肌细胞组织片。在本研究中，我们报告了在低氧条件下，HAP干细胞分化为肌钙蛋白阳性的心肌细胞的比率比在常氧条件下更高。低氧不影响分化为其他类型的细胞。为了将来将HAP干细胞用于心肌再生，低氧应该会提高分化的速度，从而为患者提供更多的机会使用他们自己的HAP干细胞，这些干细胞很容易获得。J.细胞。生物化学。2017年118：554-558。©2016 Wiley期刊，Inc.
We have previously demonstrated that the neural stem‐cell marker nestin is expressed in hair‐follicle stem cells located in the bulge area which are termed hair‐follicle‐associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15‐negative and nestin‐positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin‐expressing stem cells could effect nerve and spinal cord regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. We recently observed that isoproterenol directs HAP stem cells to differentiate to cardiac‐muscle cells in large numbers in culture compared to HAP stem cells not supplemented with isoproterenol. The addition of activin A, bone morphogenetic protein 4, and basic fibroblast growth factor, along with isoproternal, induced the cardiac muscle cells to form tissue sheets of beating heart muscle cells. In the present study, we report that, under hypoxic conditions, HAP stem cells differentiated to troponin‐positive cardiac‐muscle cells at a higher rate that under normoxic conditions. Hypoxia did not influence the differentiation to other cell types. For future use of HAP stem cells for cardiac muscle regeneration, hypoxia should enhance the rate of differentiation thereby providing patients more opportunities to use their own HAP stem cells which are easily accessible, for this purpose. J. Cell. Biochem. 118: 554–558, 2017. © 2016 Wiley Periodicals, Inc.