Purpose

Human pluripotent stem cell (hPSC)-derived dopaminergic neuron progenitor cells (DAPCs) are a potential therapy for Parkinson’s disease (PD). However, their intracranial administration raises safety concerns including uncontrolled proliferation, migration and inflammation. Here, we apply a bimodal imaging approach to investigate the fate of DAPC transplants in the rat striatum.

Procedures

DAPCs co-expressing luciferase and ZsGreen or labelled with micron-sized particles of iron oxide (MPIOs) were transplanted in the striatum of RNU rats (n = 6 per group). DAPCs were tracked in vivo using bioluminescence and magnetic resonance (MR) imaging modalities.

Results

Transgene silencing in differentiating DAPCs accompanied with signal attenuation due to animal growth rendered the bioluminescence undetectable by week 2 post intrastriatal transplantation. However, MR imaging of MPIO-labelled DAPCs showed that transplanted cells remained at the site of injection for over 120 days. Post-mortem histological analysis of DAPC transplants demonstrated that labelling with either luciferase/ZsGreen or MPIOs did not affect the ability of cells to differentiate into mature dopaminergic neurons. Importantly, labelled cells did not elicit increased glial reactivity compared to non-labelled cells.

Conclusions

In summary, our findings support the transplantation of hPSC-derived DAPCs as a safe treatment for PD.

中文翻译：

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使用非侵入性成像技术评估人类胚胎干细胞衍生的多巴胺能神经元祖细胞移植。

目的

人类多能干细胞 (hPSC) 衍生的多巴胺能神经元祖细胞 (DAPC) 是帕金森病 (PD) 的潜在疗法。然而，它们的颅内给药引起了安全问题，包括不受控制的增殖、迁移和炎症。在这里，我们应用双峰成像方法来研究 DAPC 移植在大鼠纹状体中的命运。

程序

将共表达荧光素酶和 ZsGreen 或用微米级氧化铁颗粒 (MPIO) 标记的 DAPC 移植到 RNU 大鼠的纹状体中（ 每组n = 6）。使用生物发光和磁共振 (MR) 成像方式在体内跟踪 DAPC 。

结果

分化 DAPC 中的转基因沉默伴随着由于动物生长引起的信号衰减，使得在纹状体移植后第 2 周无法检测到生物发光。然而，MPIO 标记的 DAPC 的 MR 成像显示移植的细胞在注射部位保留了 120 多天。DAPC 移植的死后组织学分析表明，用荧光素酶/ZsGreen 或 MPIO 标记不影响细胞分化为成熟多巴胺能神经元的能力。重要的是，与未标记的细胞相比，标记的细胞不会引起增加的神经胶质反应性。

结论

总之，我们的研究结果支持移植 hPSC 衍生的 DAPC 作为 PD 的安全治疗方法。