SanBio Inc. Department of Research - In vitro, USA.
SanBio Inc. Department of Research - In vitro, USA.
Neuroscience. 2024 Aug 6;552:76-88. doi: 10.1016/j.neuroscience.2024.06.015. Epub 2024 Jun 21.
Mesenchymal stromal cells (MSCs) hold therapeutic potential for neurological disorders, but their impact on neuronal activity remains unclear. We investigated the effects of SB623 cells (Notch-1 intracellular domain-transfected MSCs) and parental MSCs on human induced pluripotent stem cell (iPSC)-derived neurons using multi-electrode arrays. SB623 cells significantly increased neuronal activity and oscillation in a dose-dependent manner, surpassing astrocytes in promoting network bursts. Strikingly, glutamatergic neurons showed a rapid increase in activity and bursts compared to GABAergic neurons, suggesting glutamate release from SB623 cells. We confirmed this by finding high glutamate levels in SB623 cell conditioned medium, which were reduced by glutaminase inhibition. Glutamate release was further implicated by the reduced excitability in co-cultures with astrocytes, known glutamate scavengers. Our findings reveal a novel mechanism for MSCs: promoting neuronal activity and network formation through tonic glutamate release, with potential implications for MSC-based therapies.
间质基质细胞（MSCs）在神经紊乱疾病的治疗中有很大的潜力，但其对神经元活动的影响仍不清楚。我们使用多电极阵列研究了 SB623 细胞（ Notch-1 胞内结构域转染的 MSCs）和母代 MSCs 对人诱导多能干细胞（iPSC）衍生神经元的影响。SB623 细胞以剂量依赖性的方式显著增加神经元的活性和振荡，其促进网络爆发的能力超过了星形胶质细胞。值得注意的是，与 GABA 能神经元相比，谷氨酸能神经元的活性和爆发迅速增加，表明 SB623 细胞释放谷氨酸。我们通过发现 SB623 细胞条件培养基中谷氨酸水平升高得到了证实，而用谷氨酰胺酶抑制剂抑制谷氨酸释放可以降低其水平。与已知的谷氨酸清除剂星形胶质细胞共培养时，兴奋性降低进一步表明存在谷氨酸释放。我们的研究结果揭示了 MSCs 的一种新机制：通过持续释放谷氨酸来促进神经元的活性和网络形成，这可能对基于 MSCs 的治疗有一定的影响。
