EFFECTS OF IGF-1-OVEREXPRESSING MESENCHYMAL STROMAL CELL TRANSPLANTATION IN A MOUSE MODEL OF AMYOTROPHIC LATERAL SCLEROSIS.

Background: Amyotrophic lateral sclerosis (ALS) is an incurable disease characterized by the progressive degeneration of upper and lower motor neurons, leading to death. Increasing evidence of impaired insulin-like growth factor 1 (IGF-1) signaling pathways in ALS indicates that targeting these cascades could counteract the pathogenesis of the disease. Stem cell therapies stand out as a valuable therapeutic approach since they can be genetically modified to suppress the IGF-1 deficiency. Objectives: We investigated the therapeutic potential of mouse bone marrow-derived mesenchymal stromal cells genetically modified to overexpress IGF-1 in a mouse model of ALS. Methods: Transgenic SOD1^G93A mice were submitted to cell transplantation via intraperitoneal injections. Animals were divided into 3 groups, receiving 2 doses of 1x10⁶ MSC-IGF1, MSC-GFP, or Vehicle(DMEM/F12+DNase) at the 11^th and 15^th weeks of life. Motor function, muscle strength, and body weight were assessed once a week. Preservation of motor neurons was evaluated by immunohistochemistry. Data were analyzed by one-way ANOVA test. All procedures were approved by the Ethics Committee on the Use of Animals of the Federal University of Rio de Janeiro (CEUA nº 100/21). Results: We observed no difference in animals’ lifespan (MSC-IGF-1: 136 days; n=21; MSC-GFP: 136 days; n=22; Vehicle: 135,5 days; n=22), body weight, or functional performance between the experimental groups, for both gender. The number of motor neurons in the ventral horn of the spinal cord showed no significant difference between groups for both genders. Conclusions:Our data indicates that mBM-MSC-IGF-1 administrated intraperitoneally at weeks 11 and 15 did not present statistically relevant differences in functional tests, animals' lifespan or body weight, between the experimental groups. The quantification of motor neurons showed no statistically significant difference between the groups, indicating that there was no neuroprotective effect.