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首页> 外文期刊>Acta biomaterialia >Manipulating neural-stem-cell mobilization and migration in vitro
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Manipulating neural-stem-cell mobilization and migration in vitro

机译：体外操纵神经干细胞的动员和迁移

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Neural stem-cell transplantation is a promising strategy for the treatment of neural diseases and injuries, since the central nervous system (CNS) has a very limited capacity to repopulate the lost cells. Transplantation strategies face many difficulties including low viability, lack of control of stem-cell fate, and low levels of cell engraftment after transplantation. An alternative strategy for CNS repair without transplantation is using endogenous neural stem cells (NSCs) and precursor cells. Hepatocyte growth factor (HGF), a pleiotropic cytokine of mesenchymal origin, exerts a strong chemoattractive effect on stem cells. Leukemia inhibitory factor (LIF), a key regulator for stem-cell proliferation, mobilization, and fate choices, is currently being characterized for endogenous NSC manipulation for brain regeneration. In this study, HGF and LIF have been loaded into hydrogels and degradable nanoparticles, respectively, for sustained, long-term, localized delivery. We examine the use of HGF-loaded hydrogels and LIF-loaded nanoparticles for manipulating migration and mobilization of human NSCs in vitro. The combination of LIF-loaded nanoparticles and HGF-loaded hydrogels significantly mobilized hNSCs and promoted their migration in vitro. Studies are in progress to evaluate endogenous NSC mobilization and migration in vivo with simultaneous, controlled delivery of LIF at the natural reservoir of endogenous NSCs and HGF at the injury or disease site for in situ tissue regeneration.
机译：神经干细胞移植是治疗神经疾病和损伤的一种有前途的策略，因为中枢神经系统（CNS）再生丢失细胞的能力非常有限。移植策略面临许多困难，包括生存能力低，对干细胞命运的控制不足以及移植后细胞移植水平低。无需移植的CNS修复的另一种策略是使用内源性神经干细胞（NSC）和前体细胞。肝细胞生长因子（HGF）是间充质来源的多效性细胞因子，对干细胞具有强大的化学吸引作用。白血病抑制因子（LIF）是干细胞增殖，动员和命运选择的关键调节剂，目前已被表征为内源性NSC进行大脑再生。在这项研究中，HGF和LIF已分别装载到水凝胶和可降解纳米颗粒中，以实现持续，长期，局部递送。我们研究了使用HGF负载的水凝胶和LIF负载的纳米粒子在体外操纵人NSC的迁移和动员。载有LIF的纳米颗粒和载有HGF的水凝胶的组合可显着动员hNSC，并促进其在体外的迁移。研究正在评估内源性NSC在体内的动员和迁移，同时在内源性NSC的天然储库中同时控制地递送LIF和在损伤或疾病部位的HGF进行原位组织再生。

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