Bioreactor-produced iPSCs-derived dopaminergic neuron-containing neural microtissues innervate and normalize rotational bias in a dose-dependent manner in a Parkinson rat model

生物反应器产生的含有 iPSC 衍生的多巴胺能神经元的神经微组织在帕金森大鼠模型中以剂量依赖性方式支配和正常化旋转偏差

阅读:3
作者:Nicolas Prudon, Lucía Cordero-Espinoza, Myriam Abarkan, Basile Gurchenkov, Chloé Morel, Marilyn Lepleux, Valérie De Luca, Maxime Lartigue, Hélène Cabanas, Nadège Pujol, Loanne Milvoy, Pauline Morand, Fabien Moncaubeig, Hélène Wurtz, Léa Poinçot, Maëlle De Marco, Agathe Jonckeau, Justine Pletenka, El

Abstract

A breadth of preclinical studies now support the rationale of pluripotent stem cell-derived cell replacement therapies to alleviate motor symptoms in Parkinsonian patients. Replacement of the primary dysfunctional cell population in the disease, i.e. the A9 dopaminergic neurons, is the major focus of these therapies. To achieve this, most therapeutical approaches involve grafting single-cell suspensions of DA progenitors. However, most cells die during the transplantation process, as cells face anoïkis. One potential solution to address this challenge is to graft solid preparations, i.e. adopting a 3D format. Cryopreserving such a format remains a major hurdle and is not exempt from causing delays in the time to effect, as observed with cryopreserved single-cell DA progenitors. Here, we used a high-throughput cell-encapsulation technology coupled with bioreactors to provide a 3D culture environment enabling the directed differentiation of hiPSCs into neural microtissues. The proper patterning of these neural microtissues into a midbrain identity was confirmed using orthogonal methods, including qPCR, RNAseq, flow cytometry and immunofluorescent microscopy. The efficacy of the neural microtissues was demonstrated in a dose-dependent manner using a Parkinsonian rat model. The survival of the cells was confirmed by post-mortem histological analysis, characterised by the presence of human dopaminergic neurons projecting into the host striatum. The work reported here is the first bioproduction of a cell therapy for Parkinson's disease in a scalable bioreactor, leading to a full behavioural recovery 16 weeks after transplantation using cryopreserved 3D format.

特别声明

1、本文转载旨在传播信息,不代表本网站观点,亦不对其内容的真实性承担责任。

2、其他媒体、网站或个人若从本网站转载使用,必须保留本网站注明的“来源”,并自行承担包括版权在内的相关法律责任。

3、如作者不希望本文被转载,或需洽谈转载稿费等事宜,请及时与本网站联系。

4、此外,如需投稿,也可通过邮箱info@biocloudy.com与我们取得联系。