Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Commun Biol. 2022 Aug 10;5(1):803. doi: 10.1038/s42003-022-03736-8.
Expectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under the control of enhanced synaptic activity-responsive element (E-SARE), a potent neuronal activity-dependent synthetic promoter, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we found that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI.
神经干细胞/祖细胞(NS/PC)移植作为脊髓损伤(SCI)治疗方法的期望正在增加。然而,移植细胞是否以及如何融入宿主神经回路并有助于运动功能恢复仍然未知。本项目的目的是建立一种新的非侵入性体内成像系统,通过该系统可以可视化神经移植物的活性,从而同时证明移植物与宿主之间的回路水平整合,以及移植物神经元活性对宿主行为的贡献。我们将一种新设计的荧光素酶(Akaluc)引入到 NS/PC 中,该酶受增强的突触活性反应元件(E-SARE)的控制,E-SARE 是一种强大的神经元活性依赖性合成启动子,然后将这些细胞移植到 SCI 模型小鼠中。通过使用该系统,我们发现移植细胞的活性与宿主行为相整合,并受宿主神经回路输入的驱动。该非侵入性系统有望有助于阐明细胞移植治疗 SCI 的治疗机制。