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Benefits of Bone Marrow Mesenchymal Stem Cells Compared to Their Conditioned Medium in Valproic Acid-Induced Autism in Rats Publisher Pubmed



Noshadian M1 ; Ragerdi Kashani I1 ; Asadigolshan R1 ; Zarini D1 ; Ghafari N1 ; Zahedi E2 ; Pasbakhsh P1
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Authors Affiliations
  1. 1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, 1461884513, Iran
  2. 2. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Molecular Biology Reports Published:2024


Abstract

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by repetitive behaviors, a limited range of activities, and deficiencies in social communications. Bone marrow mesenchymal stem cells (BM-MSCs), which secrete factors that stimulate surrounding microenvironment, and BM-MSCs conditioned medium (BM-MSCs-CM), which contains cell-secreted products, have been speculated to hold potential as a therapy for ASD. This study aimed to compare the therapeutic effects of BM-MSCs and BM-MSCs-CM on behavioral and microglial changes in an animal model of autism induced by valproic acid (VPA). Methods and results: Pregnant Wistar rats were administered by VPA at a dose of 600 mg/kg at 12.5 days post-conception. After birth, male pups were included in the study. At 6 weeks of age, one group of rats received intranasal administration of BM-MSCs, while another group received BM-MSCs-CM. The rats were allowed to recover for 2 weeks. Behavioral tests, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry were performed. Both BM-MSCs and BM-MSCs-CM administration significantly improved some behavioral deficits. Furthermore, these treatments notably reduced Iba-1 marker associated with microgliosis. Additionally, there was a significant reduction in the expression of pro-inflammatory cytokines IL-1β and IL-6, and an increase in the levels of the anti-inflammatory cytokine IL-10 in rats administered by BM-MSCs and BM-MSCs-CM. Conclusions: Post-developmental administration of BM-MSCs and BM-MSCs-CM can ameliorate prenatal neurodevelopmental deficits, restore cognitive and social behaviors, and modulate microglial and inflammatory markers. Results indicated that the improvement rate was higher in the BM-MSCs group than BM-MSCs-CM group. © The Author(s), under exclusive licence to Springer Nature B.V. 2024.
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