Carvalho Sofia, Santos Juliana Inês, Moreira Luciana, Gonçalves Mariana, David Hugo, Matos Liliana, Encarnação Marisa, Alves Sandra, Coutinho Maria Francisca
Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal.
Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal.
Biomedicines. 2023 Apr 21;11(4):1234. doi: 10.3390/biomedicines11041234.
Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders; the neurological symptoms are currently incurable, even in the cases where a disease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every patient-derived cell recapitulates relevant disease features. For the neuronopathic forms of MPSs, for example, this is particularly evident because of the obvious inability to access live neurons. This scenario changed significantly with the advent of induced pluripotent stem cell (iPSC) technologies. From then on, a series of differentiation protocols to generate neurons from iPSC was developed and extensively used for disease modeling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPSs and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analyses. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also hypothesize on a tempting alternative to establish MPS patient-derived neuronal cells in a much more expedite way, by taking advantage of the existence of a population of multipotent stem cells in human dental pulp to establish mixed neuronal and glial cultures.
尽管进行了广泛的研究，但糖胺聚糖（GAGs）的积累与患有各种形式黏多糖贮积症（MPSs）的患者所表现出的临床特征之间的联系仍有待进一步阐明。对于这些疾病的神经病理学来说尤其如此；目前，即使在存在针对特定疾病的治疗方法的情况下，神经症状仍然无法治愈。了解驱动该发病机制的分子机制的最佳方法之一是分析患者来源的细胞。然而，并非每个患者来源的细胞都能重现相关的疾病特征。例如，对于神经元病变形式的MPSs，由于明显无法获取活神经元，这一点尤为明显。随着诱导多能干细胞（iPSC）技术的出现，这种情况发生了显著变化。从那时起，一系列从iPSC生成神经元的分化方案被开发出来，并广泛用于疾病建模。目前，已经为几种MPSs生成了人类iPSC和iPSC衍生的细胞模型，并从对它们的分析中学到了很多经验教训。在这里，我们回顾了大多数这些研究，不仅列出了目前可用的MPS iPSC系及其衍生模型，还总结了它们是如何生成的，以及不同研究小组从分析中收集到的主要信息。最后，考虑到iPSC生成是一个费力/昂贵的方案，并且存在重大局限性，我们还设想了一种诱人的替代方法，即利用人类牙髓中多能干细胞群体的存在来建立混合神经元和神经胶质细胞培养物，以更快速的方式建立MPS患者来源的神经元细胞。
