Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms
Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms
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DOI：
10.1172/jci59251
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发表时间：
2012-01-01
影响因子：
15.9
通讯作者：
Ueda, Minoru
中科院分区：
文献类型：
--
作者：
Sakai, Kiyoshi;Yamamoto, Akihito;Ueda, Minoru
脊髓损伤（SCI）通常会导致神经元和神经胶质细胞的丢失以及损伤后轴突再生受限，从而导致持续的功能缺陷。在这里，我们报告，人牙髓干细胞移植到完全横断的成年大鼠脊髓导致后肢运动功能的显着恢复。移植人骨髓基质细胞或皮肤来源的成纤维细胞导致运动功能的恢复明显减少。人牙髓干细胞具有三种主要的神经再生活性。首先，它们抑制SCI诱导的神经元、星形胶质细胞和少突胶质细胞的凋亡，这改善了神经元细丝和髓鞘的保存。其次，它们通过旁分泌机制直接抑制多种轴突生长抑制剂，包括硫酸软骨素蛋白聚糖和髓鞘相关糖蛋白，促进横断轴突的再生。最后，在脊髓损伤的极端条件下，它们通过分化成成熟的少突胶质细胞来取代丢失的细胞。我们的数据表明，牙源性干细胞可能通过细胞自主和旁分泌神经再生活动为治疗SCI提供治疗益处。
Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.