Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, ARB Suite 2116, 1406 South Coulter Street, Amarillo, TX, 79106, USA.
Cell Mol Neurobiol. 2023 Jul;43(5):2105-2127. doi: 10.1007/s10571-022-01291-8. Epub 2022 Oct 6.
Astrocytes have been implicated in the onset and complication of various central nervous system (CNS) injuries and disorders. Uncontrolled astrogliosis (gliosis), while a necessary process for recovery after CNS trauma, also causes impairments in CNS performance and functions. The ability to preserve astrocyte health and better regulate the gliosis process could play a major role in controlling damage in the aftermath of acute insults and during chronic dysfunction. Here in, we demonstrate the ability of dental pulp-derived stem cells (DPSCs) in protecting the health of astrocytes during induced gliosis. First of all, we have characterized the expression of genes in primary astrocytes that are relevant to the pathological conditions of CNS by inducing gliosis. Subsequently, we found that astrocytes co-cultured with DPSCs reduced ROS production, NRF2 and GCLM expressions, mitochondrial membrane potential, and mitochondrial functions compared to the astrocytes that were not co-cultured with DPSCs in gliosis condition. In addition, hyperactive autophagy was also decreased in astrocytes that were co-cultured with DPSCs compared to the astrocytes that were not co-cultured with DPSCs during gliosis. This reversal and mitigation of gliosis in astrocytes were partly due to induction of neurogenesis in DPSCs through enhanced expressions of the neuronal genes like GFAP, NeuN, and Synapsin in DPSCs and by secretion of higher amounts of neurotropic factors, such as BDNF, GDNF, and TIMP-2. Protein-Protein docking analysis suggested that BDNF and GDNF can bind with CSPG4 and block the downstream signaling. Together these findings demonstrate novel functions of DPSCs to preserve astrocyte health during gliosis.
星形胶质细胞被认为与各种中枢神经系统 (CNS) 损伤和疾病的发生和并发症有关。失控的星形胶质细胞增生（胶质增生）虽然是 CNS 创伤后恢复的必要过程，但也会导致 CNS 性能和功能受损。保持星形胶质细胞健康和更好地调节胶质增生过程的能力可能在控制急性损伤后的损伤和慢性功能障碍中发挥重要作用。在这里，我们证明了牙髓干细胞 (DPSC) 在诱导胶质增生期间保护星形胶质细胞健康的能力。首先，我们通过诱导胶质增生来表征原代星形胶质细胞中与 CNS 病理状况相关的基因表达。随后，我们发现与未与 DPSCs 共培养的星形胶质细胞相比，与 DPSCs 共培养的星形胶质细胞在胶质增生条件下 ROS 产生、NRF2 和 GCLM 表达、线粒体膜电位和线粒体功能降低。此外，与未与 DPSCs 共培养的星形胶质细胞相比，与 DPSCs 共培养的星形胶质细胞中的过度活跃自噬也减少了。星形胶质细胞中的这种胶质增生的逆转和缓解部分归因于通过增强 DPSCs 中的神经元基因如 GFAP、NeuN 和 Synapsin 的表达以及通过分泌更高量的神经营养因子，如 BDNF、GDNF 和 TIMP-2，从而诱导 DPSCs 中的神经发生。蛋白-蛋白对接分析表明，BDNF 和 GDNF 可以与 CSPG4 结合并阻断下游信号。这些发现共同表明了 DPSCs 在胶质增生过程中保护星形胶质细胞健康的新功能。
