Chandrasekaran Abinaya, Thomsen Barbara Blicher, Agerholm Jørgen Steen, Pessôa Laís Vicari de Figueiredo, Godoy Pieri Naira Caroline, Sabaghidarmiyan Vahideh, Langley Katarina, Kolko Miriam, de Andrade André Furugen Cesar, Bressan Fabiana Fernandes, Hyttel Poul, Berendt Mette, Freude Kristine
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Front Vet Sci. 2021 Nov 4;8:725386. doi: 10.3389/fvets.2021.725386. eCollection 2021.
Domestic dogs are superior models for translational medicine due to greater anatomical and physiological similarities with humans than rodents, including hereditary diseases with human equivalents. Particularly with respect to neurodegenerative medicine, dogs can serve as a natural, more relevant model of human disease compared to transgenic rodents. Herein we report attempts to develop a canine-derived model for neurodegenerative diseases through the generation of induced pluripotent stem cells from a 14-year, 9-month-old female West Highland white terrier with mild cognitive impairment (MCI). Canine induced pluripotent stem cells-like cells (ciPSCLC) were generated using human OSKM and characterized by positive expression of pluripotency markers. Due to inefficient viral vector silencing we refer to them as ciPSCLCs. Subsequently, the ciPSCLC were subjected to neural induction according to two protocols both yielding canine neural progenitor cells (cNPCs), which expressed typical NPC markers. The cNPCs were cultured in neuron differentiation media for 3 weeks, resulting in the derivation of morphologically impaired neurons as compared to iPSC-derived human counterparts generated in parallel. The apparent differences encountered in this study regarding the neural differentiation potential of ciPSCLC reveals challenges and new perspectives to consider before using the canine model in translational neurological studies.
与啮齿动物相比，家犬在解剖学和生理学上与人类有更多相似之处，包括存在与人类等效的遗传性疾病，因此是转化医学的优越模型。特别是在神经退行性疾病医学方面，与转基因啮齿动物相比，犬类可作为人类疾病更自然、更相关的模型。在此，我们报告了通过从一只14岁9个月大、患有轻度认知障碍（MCI）的雌性西高地白梗犬生成诱导多能干细胞，尝试开发一种用于神经退行性疾病的犬源模型。使用人类OSKM生成了犬诱导多能干细胞样细胞（ciPSCLC），并通过多能性标志物的阳性表达进行了表征。由于病毒载体沉默效率低下，我们将它们称为ciPSCLCs。随后，根据两种方案对ciPSCLC进行神经诱导，均产生了表达典型NPC标志物的犬神经祖细胞（cNPC）。将cNPC在神经元分化培养基中培养3周，与同时生成的iPSC来源的人类对应物相比，产生了形态受损的神经元。本研究中在ciPSCLC的神经分化潜能方面遇到的明显差异揭示了在转化神经学研究中使用犬类模型之前需要考虑的挑战和新观点。
