Early detection of structural abnormalities and cytoplasmic accumulation of TDP-43 in tissue-engineered skins derived from ALS patients.
Early detection of structural abnormalities and cytoplasmic accumulation of TDP-43 in tissue-engineered skins derived from ALS patients.
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DOI：
10.1186/s40478-014-0181-z
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发表时间：
2015-01-31
影响因子：
7.1
通讯作者：
Gros-Louis F
中科院分区：
文献类型：
--
作者：
Paré B;Touzel-Deschênes L;Lamontagne R;Lamarre MS;Scott FD;Khuong HT;Dion PA;Bouchard JP;Gould P;Rouleau GA;Dupré N;Berthod F;Gros-Louis F
肌萎缩侧索硬化症(ALS)是一种成人发病的疾病，其特征是大脑和脊髓运动神经元的选择性变性，逐渐导致瘫痪和死亡。目前ALS的诊断是基于对相关症状的临床评估。在ALS中观察到的临床表现在相当数量的运动神经元变性后出现在病程中相对较晚。因此，疾病修正疗法的识别和开发是困难的。因此，迫切需要新的策略来早期诊断神经退行性变，监测疾病进展并评估对现有和未来治疗的反应。事实上，包括肌萎缩侧索硬化症在内的许多神经疾病都伴随着皮肤变化，这些变化往往在神经症状出现之前就出现了。为了产生一种创新的基于人类的模型，以便于识别与疾病相关的预测性生物标志物，我们开发了一种独特的ALS组织工程皮肤模型(ALS-TES)，该模型源于患者自己的细胞。ALS-TES表现出许多显著的特征，包括表皮分化异常、真皮-表皮连接异常、分层、角质形成细胞浸润、胶原解体和胞浆TDP-43包涵体。值得注意的是，在携带GGGGCC DNA重复扩增的症状前C9orf72连锁ALS患者中，发现了这些在ALS来源的皮肤中独有的异常皮肤缺陷。因此，我们的ALS皮肤模型可以代表可再生的人体组织来源，快速和容易地访问，以更好地了解这种疾病的生理病理机制，促进疾病特异性生物标志物的识别，并开发用于早期诊断和疾病监测的创新工具。本文的在线版本(doi：10.1186/s40478-0140181-z)包含补充材料，授权用户可以使用。
Amyotrophic lateral sclerosis (ALS) is an adult-onset disease characterized by the selective degeneration of motor neurons in the brain and spinal cord progressively leading to paralysis and death. Current diagnosis of ALS is based on clinical assessment of related symptoms. The clinical manifestations observed in ALS appear relatively late in the disease course after degeneration of a significant number of motor neurons. As a result, the identification and development of disease-modifying therapies is difficult. Therefore, novel strategies for early diagnosis of neurodegeneration, to monitor disease progression and to assess response to existing and future treatments are urgently needed. Factually, many neurological disorders, including ALS, are accompanied by skin changes that often precede the onset of neurological symptoms. Aiming to generate an innovative human-based model to facilitate the identification of predictive biomarkers associated with the disease, we developed a unique ALS tissue-engineered skin model (ALS-TES) derived from patient’s own cells. The ALS-TES presents a number of striking features including altered epidermal differentiation, abnormal dermo-epidermal junction, delamination, keratinocyte infiltration, collagen disorganization and cytoplasmic TDP-43 inclusions. Remarkably, these abnormal skin defects, uniquely seen in the ALS-derived skins, were detected in pre-symtomatic C9orf72-linked ALS patients carrying the GGGGCC DNA repeat expansion. Consequently, our ALS skin model could represent a renewable source of human tissue, quickly and easily accessible to better understand the physiopathological mechanisms underlying this disease, to facilitate the identification of disease-specific biomarkers, and to develop innovative tools for early diagnosis and disease monitoring. The online version of this article (doi:10.1186/s40478-014-0181-z) contains supplementary material, which is available to authorized users.
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影响因子：
3.4
作者：
Clos AL;Kayed R;Lasagna-Reeves CA
通讯作者：
Lasagna-Reeves CA
DOI：
10.1016/j.mcn.2013.07.007
发表时间：
2013-09
期刊：
Molecular and cellular neurosciences
影响因子：
--
作者：
Burkhardt MF;Martinez FJ;Wright S;Ramos C;Volfson D;Mason M;Garnes J;Dang V;Lievers J;Shoukat-Mumtaz U;Martinez R;Gai H;Blake R;Vaisberg E;Grskovic M;Johnson C;Irion S;Bright J;Cooper B;Nguyen L;Griswold-Prenner I;Javaherian A
通讯作者：
Javaherian A
DOI：
10.1073/pnas.1202922109
发表时间：
2012-04-10
影响因子：
11.1
作者：
Bilican, Bilada;Serio, Andrea;Chandran, Siddharthan
通讯作者：
Chandran, Siddharthan
影响因子：
16.2
作者：
Kaplan A;Spiller KJ;Towne C;Kanning KC;Choe GT;Geber A;Akay T;Aebischer P;Henderson CE
通讯作者：
Henderson CE
影响因子：
5.3
作者：
Lorenzl, Stefan;Narr, Sabine;Beal, M. Flint
通讯作者：
Beal, M. Flint