Jiangsu Clinical Medicine Centre of Tissue Engineering and Nerve Injury Repair, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, People's Republic of China.
Department of Neurosurgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.
Stem Cells. 2019 Oct;37(10):1344-1356. doi: 10.1002/stem.3060. Epub 2019 Aug 5.
Due to the limited capacity of brain tissue to self-regenerate after traumatic brain injury (TBI), the mobilization of endogenous neural stem cells (NSCs) is a popular research topic. In the clinic, the neurogenic abilities of adults versus neonates vary greatly, which is likely related to functional differences in NSCs. Recent studies have demonstrated that the molecules secreted from astrocytes play important roles in NSC fate determination. In this study, conditioned media (CM) derived from neonatal or adult rat astrocytes, which were unstimulated or stimulated by lipopolysaccharide (LPS), were prepared to treat NSCs. Our results revealed that neonatal rat astrocytes can significantly promote the proliferation of NSCs, compared with adult rat astrocytes, regardless of whether or not they were stimulated by LPS. Furthermore, we used mass spectrometry to detect the constituents of the CM from each group. We analyzed and screened for a protein, Tenascin-C (TNC), which was highly expressed in the neonatal group but poorly expressed in the adult group. We found that TNC can bind to the NSC surface epidermal growth factor receptor and promote proliferation through the PI3K-AKT pathway in vitro. Additionally, we confirmed in vivo that TNC can promote damage repair in a rat model of TBI, through enhancing the proliferation of endogenous NSCs. We believe that these findings provide a mechanistic understanding of why neonates show better neuroregenerative abilities than adults. This also provides a potential future therapeutic target, TNC, for injury repair after TBI. Stem Cells 2019;37:1344-1356.
由于脑外伤（TBI）后脑组织自身再生的能力有限，因此动员内源性神经干细胞（NSC）是一个热门的研究课题。在临床上，成人和新生儿的神经发生能力有很大的不同，这可能与 NSC 的功能差异有关。最近的研究表明，星形胶质细胞分泌的分子在 NSC 命运决定中发挥着重要作用。在这项研究中，制备了未受刺激或受脂多糖（LPS）刺激的新生或成年大鼠星形胶质细胞的条件培养基（CM）来处理 NSCs。我们的结果表明，与成年大鼠星形胶质细胞相比，新生大鼠星形胶质细胞可以显著促进 NSCs 的增殖，无论它们是否受到 LPS 的刺激。此外，我们使用质谱法检测了每组 CM 的成分。我们分析和筛选了一种在新生组中高度表达而在成年组中表达水平较低的蛋白，即 tenascin-C（TNC）。我们发现 TNC 可以与 NSC 表面的表皮生长因子受体结合，并通过体外的 PI3K-AKT 通路促进增殖。此外，我们在体内证实 TNC 可以通过增强内源性 NSCs 的增殖，促进 TBI 大鼠模型的损伤修复。我们认为这些发现为为什么新生儿比成年人具有更好的神经再生能力提供了机制上的理解。这也为 TBI 后损伤修复提供了一个潜在的治疗靶点 TNC。Stem Cells 2019;37:1344-1356.
