人Muse细胞诱导分化为神经前体细胞及功能性神经元并修复脊髓损伤

After spinal cord injury, the apoptosis and necrosis of neurons and glial cells make the axon regeneration difficult. It`s essential to replace the dead and injuried nerve cells in order to promote the nerve regeneration and functional reestablishment. Multilineage differentiating stress enduring (Muse) cells are a newly discovered unique subpopulation of cells that distribute in the mesenchyme expressing multiple pluripotency markers. They have self-renewal properties and the capacity of differentiating into all of the three germ layers with no teratoma formation. These qualities make them promising candidates for tissue engineered seeding cells to repair spinal cord injury. Our previous studies have successfully isolated Muse cells from human bone marrow and then induced them into neural precursor cells (Muse-NPCs) in vitro. In this proposal the directional pluripotent stem cell characteristics of Muse-NPCs will be identified followed by inducing to neurons (MNiN). The morphological and functional characteristics of MNiN will be observed. In vivo Muse-NPCs will be transplanted to repair spinal cord injury model in rats. The survival, migration, differentiation and integration of the transplanted cells will be observed as well as the spinal nerve regeneration and functional recovery. Muse cells could be expected to improve the effect of spinal cord injury repairing by increasing the differentiation rate of nerve tissue cells. This study will shed light on the application of Muse cells in the treatment of other injuries of the central nerve system.

脊髓损伤后，神经元和神经胶质细胞大量凋亡和坏死，导致轴突再生困难，为了促进神经再生和功能重建，需要补充神经组织细胞。多系分化持续应激（Muse）细胞是新近发现的存在于间充质中具有多能干细胞特性的独特亚群，能自我更新及向三个胚层分化，取材方便，体内不成瘤，有希望成为组织工程修复脊髓损伤的种子细胞。我们前期研究已成功的从人骨髓中分离出Muse细胞，经初步诱导为含神经前体细胞标志物的细胞球（Muse-NPCs）。本课题拟在此基础上对Muse-NPCs的定向多能干细胞特性进行鉴定，并进一步诱导分化为神经元（MNiN），观察MNiN的形态学和功能学特征；体内移植Muse-NPCs修复大鼠脊髓损伤模型，观察细胞的存活、迁移、分化和整合情况，以及损伤脊髓的神经再生和功能恢复情况，希望Muse细胞能通过提高神经细胞的分化率来改善脊髓损伤的修复效果。本研究可为Muse细胞治疗中枢神经系统损伤提供有益的借鉴。

脊髓损伤后，神经元和神经胶质细胞大量凋亡和坏死，导致轴突再生困难，为了促进神经再生和功能重建，需要补充神经组织细胞。本课题利用新近发现的存在于间充质中的多能干细胞——多系分化持续应激（Muse）细胞作为种子细胞，观察其向神经组织细胞分化的特性以及移植修复脊髓损伤的效果。结果显示从人骨髓中成功分离Muse细胞，经初步诱导为含神经前体细胞标志物的细胞球（Muse-NPCs）；Muse-NPCs细胞球具有神经干细胞特性，经诱导培养基培养后可以向神经元、少突胶质细胞和星形胶质细胞分化，并具有生物学功能。体内移植Muse-NPCs修复大鼠脊髓损伤模型，发现Muse-NPCs能够分化成神经元和少突胶质细胞；通过调节局部微环境降低反应性星形胶质细胞的活性，有利于神经纤维向损伤区域的迁移；Muse-NPCs移植体内后有效促进大鼠动功能的恢复。本研究可为Muse细胞治疗中枢神经系统损伤提供有益的借鉴。