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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves.
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Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves.

机译:植入的毛囊干细胞形成雪旺细胞,支持修复受损的周围神经。

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摘要

The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, also is expressed in follicle stem cells and their immediate, differentiated progeny. The fluorescent protein GFP, whose expression is driven by the nestin regulatory element in transgenic mice, served to mark the follicle cell fate. The pluripotent nestin-driven GFP stem cells are positive for the stem cell marker CD34 but negative for keratinocyte marker keratin 15, suggesting their relatively undifferentiated state. These cells can differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In vivo studies show the nestin-driven GFP hair follicle stem cells can differentiate into blood vessels and neural tissue after transplantation to the subcutis of nude mice. Equivalent hair follicle stem cells derived from transgenic mice with beta-actin-driven GFP implanted into the gap region of a severed sciatic nerve greatly enhance the rate of nerve regeneration and the restoration of nerve function. The follicle cells transdifferentiate largely into Schwann cells, which are known to support neuron regrowth. Function of the rejoined sciatic nerve was measured by contraction of the gastrocnemius muscle upon electrical stimulation. After severing the tibial nerve and subsequent transplantation of hair follicle stem cells, walking print length and intermediate toe spread significantly recovered, indicating that the transplanted mice recovered the ability to walk normally. These results suggest that hair follicle stem cells provide an important, accessible, autologous source of adult stem cells for regenerative medicine.
机译:毛囊隆起区域是活跃生长的多能成年干细胞的丰富且容易获得的来源。巢蛋白是神经干细胞的蛋白质标记物,也在卵泡干细胞及其直接分化的子代中表达。荧光蛋白GFP在转基因小鼠中由Nestin调控元件驱动表达,可标记卵泡细胞的命运。多能巢蛋白驱动的GFP干细胞对干细胞标记CD34呈阳性,但对角质形成细胞标记角蛋白15呈阴性,表明它们相对未分化的状态。这些细胞可以在体外分化为神经元,神经胶质细胞,角质形成细胞,平滑肌细胞和黑素细胞。体内研究表明,巢蛋白驱动的GFP毛囊干细胞移植到裸鼠皮下组织后可以分化为血管和神经组织。将具有β-肌动蛋白驱动的GFP植入到切断的坐骨神经间隙区域的转基因小鼠衍生的等效毛囊干细胞极大地提高了神经再生的速度和神经功能的恢复。卵泡细胞大量分化为雪旺细胞,后者可支持神经元再生。通过电刺激腓肠肌收缩来测量再坐骨神经的功能。在切断胫神经并随后移植毛囊干细胞后,步行印记的长度和中间脚趾的传播得以明显恢复,这表明移植的小鼠恢复了正常行走的能力。这些结果表明,毛囊干细胞为再生医学提供了成人干细胞的重要,可接近的自体来源。

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