Amoh Yasuyuki, Li Lingna, Katsuoka Kensei, Hoffman Robert M
AntiCancer, Inc., San Diego, California 92111, USA.
Cell Cycle. 2008 Jun 15;7(12):1865-9. doi: 10.4161/cc.7.12.6056. Epub 2008 Jun 2.
The mouse hair follicle is an easily accessible source of actively growing, pluripotent adult stem cells. C57BL transgenic mice, labeled with the fluorescent protein GFP, afforded follicle stem cells whose fate could be followed when transferred to recipient animals. These cells appear to be relatively undifferentiated since they are positive for the stem cell markers nestin and CD34 but negative for the keratinocyte marker keratin 15. These hair follicle stem cells can differentiate into neurons, glia, keratinocytes, smooth muscle cells and melanocytes in vitro. Implanting hair follicle stem cells into the gap region of severed sciatic or tibial nerves greatly enhanced the rate of nerve regeneration and restoration of nerve function. The transplanted follicle cells transdifferentiated mostly into Schwann cells, which are known to support neuron regrowth. The treated mice regained the ability to walk essentially normally. In the present study, we severed the thoracic spinal chord of C57BL/6 immunocompetent mice and transplanted GFP-expressing hair follicle stem cells to the injury site. Most of the transplanted cells also differentiated into Schwann cells that apparently facilitated repair of the severed spinal cord. The rejoined spinal cord reestablished extensive hind-limb locomotor performance. These results suggest that hair follicle stem cells can promote the recovery of spinal cord injury. Thus, hair follicle stem cells provide an effective accessible, autologous source of stem cells for the promising treatment of peripheral nerve and spinal cord injury.
小鼠毛囊是易于获取的、活跃生长的多能成体干细胞来源。用荧光蛋白GFP标记的C57BL转基因小鼠可提供毛囊干细胞,将其转移到受体动物体内时可追踪其命运。这些细胞似乎相对未分化,因为它们对干细胞标志物巢蛋白和CD34呈阳性,但对角质形成细胞标志物角蛋白15呈阴性。这些毛囊干细胞在体外可分化为神经元、神经胶质细胞、角质形成细胞、平滑肌细胞和黑素细胞。将毛囊干细胞植入切断的坐骨神经或胫神经的间隙区域可大大提高神经再生速率和神经功能恢复。移植的毛囊细胞大多转分化为雪旺细胞,已知雪旺细胞可支持神经元再生。接受治疗的小鼠基本恢复了正常行走能力。在本研究中,我们切断了C57BL/6免疫活性小鼠的胸段脊髓,并将表达GFP的毛囊干细胞移植到损伤部位。大多数移植细胞也分化为雪旺细胞,这显然促进了切断脊髓的修复。重新连接的脊髓恢复了广泛的后肢运动能力。这些结果表明,毛囊干细胞可促进脊髓损伤的恢复。因此,毛囊干细胞为周围神经和脊髓损伤的有前景治疗提供了一种有效、可获取的自体干细胞来源。