Evaluating the Therapeutic Effects of Mesenchymal Stem Cell Therapy in Huntington’s Rodent Models

Huntington’s disease is a fatal neurodegenerative disorder caused by CAG repeat expansion in the HTT gene, leading to progressive motor impairment, cognitive decline, and neuronal loss in the striatum and cortex. Current treatments are limited to symptom management, requiring the need for disease-modifying regenerative therapies. This review examines whether mesenchymal stem cell (MSC) therapy represents a promising therapeutic strategy for Huntington’s disease. Evidence from preclinical rodent studies consistently demonstrates that MSC transplantation improves motor coordination, preserves striatal volume, and enhances neuronal survival. These effects are largely attributed to the secretion of neurotrophic factors, reduction of neuroinflammation, and support of tissue repair. MSCs are particularly attractive for regenerative medicine because they possess immunomodulatory properties and can release a wide range of protective signaling molecules that promote neuronal survival and reduce inflammatory damage. In several experimental models of Huntington’s disease, transplanted MSCs have been shown to migrate toward injured brain regions and release trophic factors that help stabilize neuronal networks and slow neurodegeneration. However, therapeutic outcomes vary depending on factors such as the disease model used, the stage of disease at the time of treatment, and the route of cell administration. These variables influence the survival, integration, and functional impact of transplanted cells. Overall, these findings highlight MSC therapy as a promising approach to slowing neurodegeneration in Huntington’s disease and support further optimization and translation of MSC-based therapies for Huntington’s disease and other neurodegenerative disorders.