Non-mammalian growth factor formulations for human nervous system regenerative medicine

人类和其他哺乳动物再生神经和替换受伤或受损神经元的能力有限。相比之下，其他脊椎动物被赋予了上级再生多个器官的能力;在四足动物中，蝾螈和蝾螈等水生蝾螈具有最大的再生谱。例如，有尾目两栖动物如美西蝾螈（Ambystoma mexicanum）具有在整个生命过程中向大脑添加新神经元的能力[1]，再生周围神经损伤[2]和机械损伤后的脊髓[3，4]。最近在了解蝾螈的再生和发育过程方面取得的进展对于能够推动人类哺乳动物的再生具有至关重要的作用。因此，本项目的目的是开发基于非哺乳动物生长因子的治疗人类神经系统疾病的新药。具体来说，我们打算将联合收割机在理解蝾螈启发的再生方面的新进展与先进的制药技术相结合，以治疗神经系统疾病。我们将：（i）鉴定在人细胞系中有效的与美西蝾螈中优异再生相关的非哺乳动物生长因子;（ii）用鉴定的生物相容性生长因子制造控释制剂;和（iii）体外评估制剂的促再生影响。参考文献：[1] Maden M，Manwell LA，Ormerod BK. Proliferation zones in the axolotl brain and regeneration of the telencephalon.神经发育2013;8：1。[2][10]杨文，杨文.蝾螈周围神经再生与功能恢复过程中组织结构的无标记成像。科学报告。2019;9：12641. [3]Amamoto R，洛佩斯韦尔塔VG，高桥E，戴G，格兰特AK，傅Z，Arlotta P.成年蝾螈可以再生原始神经元多样性，以应对脑损伤。eLife 2016; 5：e13998. [4]放大图片作者：Simon A.蝾螈的稳态和再生神经发生。神经学的进展。2018; 170：81-98.项目与预测药物科学和先进产品设计相一致

Humans and other mammals have limited ability to regenerate nerves and replace injured or damaged neurons. In contrast, other vertebrates are endowed with superior capacity to regenerate multiple organs; among tetrapods, aquatic salamanders such as newts and axolotls, have the largest regenerative spectrum. For example, urodele amphibians such as the axolotl (Ambystoma mexicanum) are endowed with the capacity to add new neurons to the brain throughout life [1], regenerate peripheral nerve injuries [2] and spinal cord after mechanical injury [3, 4]. Recent advances in understanding the regenerative and developmental processes in salamanders have a crucial role in being able to drive forward regeneration in human mammals.The aim of this project therefore is to develop new medicines to treat human nervous system disorders based on non-mammalian growth factors. Specifically, we intend to combine new advances in understanding regeneration inspired by salamanders with advanced pharmaceutical technologies to treat nervous system disorders. We will: (i) identify non-mammalian growth factors associated with excellent regeneration in axolotl which are effective in human cell lines; (ii) fabricate controlled release formulations with identified biocompatible growth factors and (iii) assess pro-regenerative impact of formulations in vitro. References: [1] Maden M, Manwell LA, Ormerod BK. Proliferation zones in the axolotl brain and regeneration of the telencephalon. Neural Development. 2013;8:1. [2] Uckermann O, Hirsch J, Galli R, Bendig J, Later R, Koch E, Schackert G, Steiner G, Tanaka E, Kirsch M. Label-free imaging of tissue architecture during axolotl peripheral nerve regeneration in comparison to functional recovery. Scientific Reports. 2019;9:12641. [3] Amamoto R, Lopez Huerta VG, Takahashi E, Dai G, Grant AK, Fu Z, Arlotta P. Adult axolotls can regenerate original neuronal diversity in response to brain injury. eLife. 2016; 5: e13998. [4] Joven A, Simon A. Homeostatic and regenerative neurogenesis in salamanders. Progress in Neurobiogy. 2018; 170: 81-98. Project aligned to Predictive Pharmaceutical Sciences and Advanced Product Design