Neuronal Differentiation of Cartilage-derived Stem Cells In Vitro and their Delivery to the Spinal Cord in a Mouse Model of ALS Using MRI-guided Focused Ultrasound
Year: 2020
Type: dissertation
Abstract: Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disorder for which stem cells are attractive therapeutic interventions. However, the complications of immunosuppression for allografts and invasive surgeries for blood-spinal cord barrier (BSCB) penetration have hampered their success. First, we investigated the in vitro neuronal differentiation potential of immunosuppressive, cartilage-derived stem cells (CDCSs). Next, we examined the safety and survival of intravenously injected, GFP-expressing, neuronally-differentiated CDSCs in an ALS mouse model (SOD-G93A), following MRI-guided focused ultrasound (MRIgFUS)-mediated opening of the BSCB. CDSCs’ neuronal differentiation was successful. GFP+ cells were not detected within the spinal cords of treated mice; no behavioural improvements were noted. Despite lack of efficacy, disease onset and survival in treated SOD1-G93A mice remained similar to the control SOD1-G93A mice, indicating that treatment did not hamper motor performance. This is the first study to demonstrate neuronal differentiation of CDSCs and feasibility of MRIgFUS-mediated BSCB opening in SOD1-G93A mice.
Source: TSpace (University of Toronto)
Author: Kairavi Shah
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3126496723