Polyurethane Culture Substrates Enable Long-Term Neuron Monoculture in a Human in vitro Model of Neurotrauma.
Polyurethane Culture Substrates Enable Long-Term Neuron Monoculture in a Human in vitro Model of Neurotrauma.
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DOI：
10.1089/neur.2023.0060
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发表时间：
2023
影响因子：
2.4
通讯作者：
Finan, John D.
中科院分区：
文献类型：
--
作者：
Mitevska, Angela;Santacruz, Citlally;Martin, Eric J.;Jones, Ian E.;Ghiacy, Arian;Dixon, Simon;Mostafazadeh, Nima;Peng, Zhangli;Kiskinis, Evangelos;Finan, John D.
人类诱导多能干细胞（hiPSC）衍生的细胞可以重现人类特异性病理生理学，患者特异性脆弱性和神经系统疾病中的基因-环境相互作用。因此，人类体外神经创伤模型具有推动该领域发展的巨大潜力。然而，在解决重要的生物材料挑战之前，这种潜力无法实现。在聚二甲基硅氧烷（PDMS）片上培养细胞的神经创伤牵张损伤模型的现状，其与hiPSC衍生的神经元的长期单一培养不相容。在这里，我们克服了这一挑战，在一个既定的人类体外神经创伤模型，取代聚二甲基硅氧烷与聚氨酯（PU）的高度生物相容性的形式。这种取代允许hiPSC衍生的神经元的长期单培养。它也改变了拉伸损伤的生物力学。我们量化这些变化的实验使用高速摄像和数字图像相关。我们使用有限元建模来量化培养基质的厚度、刚度和摩擦系数对膜拉伸的影响，并得出结论，摩擦系数解释了大多数观察到的生物力学变化。尽管有这些变化，我们证明了改良模型在hiPSC衍生的神经元单培养物中产生了稳健的剂量依赖性创伤表型。总之，该PU膜的引入使得可以在人体外神经创伤模型中将hiPSC衍生的神经元长期维持在单培养物中。在这样做的过程中，它通过启用独特的实验范式（例如，同基因模型）与hiPSC衍生的神经元相关。
Human induced pluripotent stem cell (hiPSC)-derived cells can reproduce human-specific pathophysiology, patient-specific vulnerability, and gene-environment interactions in neurological disease. Human in vitro models of neurotrauma therefore have great potential to advance the field. However, this potential cannot be realized until important biomaterials challenges are addressed. Status quo stretch injury models of neurotrauma culture cells on sheets of polydimethylsiloxane (PDMS) that are incompatible with long-term monoculture of hiPSC-derived neurons. Here, we overcame this challenge in an established human in vitro neurotrauma model by replacing PDMS with a highly biocompatible form of polyurethane (PU). This substitution allowed long-term monoculture of hiPSC-derived neurons. It also changed the biomechanics of stretch injury. We quantified these changes experimentally using high-speed videography and digital image correlation. We used finite element modeling to quantify the influence of the culture substrate's thickness, stiffness, and coefficient of friction on membrane stretch and concluded that the coefficient of friction explained most of the observed biomechanical changes. Despite these changes, we demonstrated that the modified model produced a robust, dose-dependent trauma phenotype in hiPSC-derived neuron monocultures. In summary, the introduction of this PU film makes it possible to maintain hiPSC-derived neurons in monoculture for long periods in a human in vitro neurotrauma model. In doing so, it opens new horizons in the field of neurotrauma by enabling the unique experimental paradigms (e.g., isogenic models) associated with hiPSC-derived neurons.
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影响因子：
64.8
作者：
Israel, Mason A.;Yuan, Shauna H.;Bardy, Cedric;Reyna, Sol M.;Mu, Yangling;Herrera, Cheryl;Hefferan, Michael P.;Van Gorp, Sebastiaan;Nazor, Kristopher L.;Boscolo, Francesca S.;Carson, Christian T.;Laurent, Louise C.;Marsala, Martin;Gage, Fred H.;Remes, Anne M.;Koo, Edward H.;Goldstein, Lawrence S. B.
通讯作者：
Goldstein, Lawrence S. B.
亨廷顿病的诱导多能干细胞：疾病模型和细胞治疗的潜力
影响因子：
5.1
作者：
Liu L;Huang JS;Han C;Zhang GX;Xu XY;Shen Y;Li J;Jiang HY;Lin ZC;Xiong N;Wang T
通讯作者：
Wang T
影响因子：
6.1
作者：
Millet, Larry J.;Stewart, Matthew E.;Gillette, Martha U.
通讯作者：
Gillette, Martha U.
影响因子：
4.2
作者：
ELLIS, EF;MCKINNEY, JS;POVLISHOCK, JT
通讯作者：
POVLISHOCK, JT
影响因子：
158.5
作者：
Mackay, Daniel F.;Russell, Emma R.;Stewart, William
通讯作者：
Stewart, William