Group of Vascular Regeneration, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Stem Cells. 2010 Feb;28(2):365-75. doi: 10.1002/stem.243.
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.
Lnk 是一种细胞内衔接蛋白，据报道，它是 c-Kit 阳性、Sca-1 阳性、谱系标记阴性（KSL）骨髓细胞增殖的负调节剂。人们认为骨髓中的 KSL 部分代表了一群造血和内皮祖细胞（EPCs）。我们在这里报告说，在体外，Lnk(-/-)KSL 细胞比 Lnk(+/+)KSL 细胞形成更多的 EPC 集落，并且表现出更高水平的内皮标记基因的表达，包括 CD105、CD144、Tie-1 和 Tie2，比其野生型对应物更高。在体内，向小鼠脊髓损伤模型中给予 Lnk(+/+)KSL 细胞可促进血管生成、星形胶质细胞增生、轴突生长和损伤后的功能恢复，而 Lnk(-/-)KSL 细胞在诱导和促进这些再生事件方面明显更有效。在损伤后第 3 天，可以在用 KSL 细胞处理的脊髓中观察到大血管，并且发现反应性星形胶质细胞沿着这些大血管迁移。我们还可以进一步表明，星形胶质细胞增生的增强似乎是与血管生成的加速同时发生的。这些发现表明，Lnk 缺失增强了 KSL 细胞向 EPC 的分化，通过加速血管生成和星形胶质细胞增生来促进受伤脊髓的后续修复。
