Santos Matilde, Moreira João A Ferreira, Santos Sónia Sá, Solá Susana
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisbon, Portugal.
Mol Neurobiol. 2025 Feb 22. doi: 10.1007/s12035-025-04774-z.
In the last two decades, stem cells (SCs) have attracted considerable interest for their research value and therapeutic potential in many fields, namely in neuroscience. On the other hand, the discovery of adult neurogenesis, the process by which new neurons are generated in the adult brain, challenged the traditional view that the brain is a static structure after development. The recent findings showing that adult neurogenesis has a significant role in brain plasticity, learning and memory, and emotional behavior, together with the fact that it is strongly dependent on several external and internal factors, have sparked more interest in this area. The mechanisms of adult neural stem cell (NSC) regulation, the physiological role of NSC-mediated neuroplasticity throughout life, and the most recent NSC-based therapeutic applications will be concisely reviewed. Noteworthy, due to their multipotency, self-renewal potential, and ability to secrete growth and immunomodulatory factors, NSCs have been mainly suggested for (1) transplantation, (2) neurotoxicology tests, and (3) drug screening approaches. The clinical trials of NSC-based therapy for different neurologic conditions are, nonetheless, mostly in the early phases and have not yet demonstrated conclusive efficacy or safety. Here, we provide an outlook of the major challenges and limitations, as well as some promising directions that could help to move toward stem cell widespread use in the treatment and prevention of several neurological disorders.
在过去二十年中，干细胞因其在许多领域（尤其是神经科学领域）的研究价值和治疗潜力而备受关注。另一方面，成体神经发生的发现，即在成人大脑中产生新神经元的过程，挑战了传统观点，即大脑在发育后是一个静态结构。最近的研究结果表明，成体神经发生在大脑可塑性、学习和记忆以及情绪行为中具有重要作用，而且它强烈依赖于多种外部和内部因素，这引发了该领域更多的关注。本文将简要综述成体神经干细胞（NSC）的调控机制、NSC介导的神经可塑性在整个生命过程中的生理作用以及基于NSC的最新治疗应用。值得注意的是，由于NSC具有多能性、自我更新潜力以及分泌生长和免疫调节因子的能力，它们主要被用于（1）移植、（2）神经毒理学测试和（3）药物筛选方法。然而，针对不同神经疾病的基于NSC治疗的临床试验大多处于早期阶段，尚未证明其确切的疗效和安全性。在此，我们展望了主要的挑战和局限性，以及一些有前景的方向，这些方向可能有助于推动干细胞在治疗和预防多种神经疾病方面的广泛应用。
