TY - JOUR

T1 - Neural Derivates of Canine Induced Pluripotent Stem Cells-Like Cells From a Mild Cognitive Impairment Dog

AU - Chandrasekaran, Abinaya

AU - Thomsen, Barbara Blicher

AU - Agerholm, Jørgen Steen

AU - Pessôa, Laís Vicari De Figueiredo

AU - Godoy Pieri, Naira Caroline

AU - Sabaghidarmiyan, Vahideh

AU - Langley, Katarina

AU - Kolko, Miriam

AU - De Andrade, André Furugen Cesar

AU - Bressan, Fabiana Fernandes

AU - Hyttel, Poul

AU - Berendt, Mette

AU - Freude, Kristine

PY - 2021

Y1 - 2021

N2 - 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 in vitro 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.

AB - 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 in vitro 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.

U2 - 10.3389/fvets.2021.725386

DO - 10.3389/fvets.2021.725386

M3 - Journal article

C2 - 34805331

VL - 8

JO - Frontiers in Veterinary Science

JF - Frontiers in Veterinary Science

SN - 2297-1769

M1 - 725386

ER -