Lnk Deletion Reinforces the Function of Bone Marrow Progenitors in Promoting Neovascularization and Astrogliosis Following Spinal Cord Injury
Lnk Deletion Reinforces the Function of Bone Marrow Progenitors in Promoting Neovascularization and Astrogliosis Following Spinal Cord Injury
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DOI：
10.1002/stem.243
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发表时间：
2010-02-01
期刊：
影响因子：
5.2
通讯作者：
Asahara, Takayuki
中科院分区：
文献类型：
--
作者：
Kamei, Naosuke;Kwon, Sang-Mo;Asahara, Takayuki
LNK是一种细胞内适配子蛋白，在c-Kit阳性、SCA-1阳性、谱系标志阴性(KSL)的骨髓细胞中被认为是一种负向增殖调节因子。小鼠骨髓中的KSL组分被认为代表了造血祖细胞和内皮祖细胞(EPC)的数量。我们在此报道，在体外，LNK(-/-)KSL细胞比LNK(+/+)KSL细胞形成更多的EPC克隆，并且比它们的野生型KSL细胞表现出更高水平的内皮标志基因，包括CD105，CD144，Tie-1和Tie2。在体内，在小鼠脊髓损伤模型中应用LNK(+/+)KSL细胞可促进损伤后血管生成、星形胶质细胞生长、轴突生长和功能恢复，其中LNK(-/-)KSL在诱导和促进这些再生事件方面明显更有效。损伤后3d，经KSL细胞处理的脊髓内可见大血管，反应性星形胶质细胞沿这些大血管迁移。我们可以进一步证明，星形胶质细胞增生症的增强似乎与血管生成的加速有关。这些发现表明，LNK缺失增强了KSL细胞对内皮祖细胞的承诺，通过加速血管生成和星形胶质细胞生长，促进了损伤脊髓的后续修复。干细胞2010；28：365-375
Lnk is an intracellular adaptor protein reported as a negative regulator of proliferation in c-Kit positive, Sca-1 positive, lineage marker-negative (KSL) bone marrow cells. The KSL fraction in mouse bone marrow is believed to represent a population of hematopoietic and endothelial progenitor cells (EPCs). We report here that, in vitro, Lnk(-/-) KSL cells form more EPC colonies than Lnk(+/+) KSL cells and show higher expression levels of endothelial marker genes, including CD105, CD144, Tie-1, and Tie2, than their wild-type counterparts. In vivo, the administration of Lnk(+/+) KSL cells to a mouse spinal cord injury model promoted angiogenesis, astrogliosis, axon growth, and functional recovery following injury, with Lnk(-/-) KSL being significantly more effective in inducing and promoting these regenerative events. At day 3 following injury, large vessels could be observed in spinal cords treated with KSL cells, and reactive astrocytes were found to have migrated along these large vessels. We could further show that the enhancement of astrogliosis appears to be caused in conjunction with the acceleration of angiogenesis. These findings suggest that Lnk deletion reinforces the commitment of KSL cells to EPCs, promoting subsequent repair of injured spinal cord through the acceleration of angiogenesis and astrogliosis. STEM CELLS 2010;28:365-375