Centro de Biología Molecular Severo Ochoa (CSIC-UAM) and Departamento de Biología Molecular, Universidad Autónoma de Madrid, Nicolás Cabrera, 1, 28049 Madrid, Spain.
Molecular Genetics Unit, Institute of Rare Diseases Research, Institute of Health Carlos III (ISCIII), Ctra. Majadahonda-Pozuelo Km 2,200, 28220 Madrid, Spain.
Int J Mol Sci. 2020 Sep 11;21(18):6662. doi: 10.3390/ijms21186662.
Friedreich's ataxia is the most common hereditary ataxia for which there is no cure or approved treatment at present. However, therapeutic developments based on the understanding of pathological mechanisms underlying the disease have advanced considerably, with the implementation of cellular models that mimic the disease playing a crucial role. Human olfactory ecto-mesenchymal stem cells represent a novel model that could prove useful due to their accessibility and neurogenic capacity. Here, we isolated and cultured these stem cells from Friedreich´s ataxia patients and healthy donors, characterizing their phenotype and describing disease-specific features such as reduced cell viability, impaired aconitase activity, increased ROS production and the release of cytokines involved in neuroinflammation. Importantly, we observed a positive effect on patient-derived cells, when frataxin levels were restored, confirming the utility of this in vitro model to study the disease. This model will improve our understanding of Friedreich´s ataxia pathogenesis and will help in developing rationally designed therapeutic strategies.
弗里德里希共济失调是最常见的遗传性共济失调，目前尚无治愈方法或批准的治疗方法。然而，基于对疾病病理机制的理解而进行的治疗开发已经取得了相当大的进展，实施模拟疾病的细胞模型发挥了关键作用。人类嗅觉外胚层间充质干细胞是一种新型模型，由于其可及性和神经发生能力，可能具有实用性。在这里，我们从弗里德里希共济失调患者和健康供体中分离和培养了这些干细胞，对其表型进行了特征描述，并描述了疾病特异性特征，例如细胞活力降低、顺乌头酸酶活性受损、活性氧产生增加以及参与神经炎症的细胞因子释放。重要的是，当恢复 frataxin 水平时，我们观察到对患者来源细胞的积极影响，证实了该体外模型在研究疾病方面的实用性。该模型将提高我们对弗里德里希共济失调发病机制的理解，并有助于制定合理设计的治疗策略。
