Effects of melatonin-pretreated adipose-derived mesenchymal stem cells (MSC) in an animal model of spinal cord injury

Abstract

Background One of the most serious nervous system diseases is spinal cord injury(SCI), which is increasing for various reasons. Although no definitive treatment has yet been identified for SCI, one possible treatment is adipose-derived stem cells(ADSCs). However, a key issue in transplantation is improving cells’ survival and function in the target tissue. Melatonin(MT) hormone with antioxidant properties can prolong cell survival and improve cell function. This study investigates the pre-conditioning of ADSCs with melatonin for enhancing the engraftment and neurological function of rats undergoing SCI. Methods 42 male Sprague–Dawley rats were divided into six groups, including Control, Sham, Model, Vehicle, and Lesion treatments A and B. After acquiring white adipose tissue, stem cells were evaluated by flow cytometry. SCI was then applied in Model, Vehicle, A, and B groups. Group A and B received ADSCs and ADSCs + melatonin, respectively, 1 week after SCI, but the vehicle received only an intravenous injection for simulation; The other groups were recruited for the behavioral test. Immunohistochemistry(IHC) was used to assess the engraftment and differentiation of ADSCs in the SCI site. Basso, Beattie, and Bresnahan's score was used to evaluate motor function between the six groups. Results Histological studies and cell count confirmed ADSCs implantation at the injury site, which was higher in the MT-ADSCs (P < 0.001). IHC revealed the differentiation of ADSCs and MT-ADSCs into neurons, astrocytes, and oligodendrocyte lineage cells, which were higher in MT-ADSCs. Functional improvement was observed in SCI + ADSCs and SCI + MT-ADSCs groups. Conclusion The pre-conditioning of ADSCs with melatonin positively affects engraftment and neuronal differentiation in SCI but does not impact performance improvement compared to the ADSCs.

Research hotspots and frontiers of preconditioning in cerebral ischemia: A bibliometric analysis

“…In addition, preconditioning with other factors has shown positive effects, including but not limited to (1) pharmacological and chemical agents, such as hydrogen sulfide [ 171 ], lipopolysaccharide [ 172 ], sevoflurane [ 173 ], melatonin [ 174 ], celastrol [ 175 ], and thrombin [ 176 ]. (2) Micronutrients, such as zinc [ 177 ], and lithium [ 178 ].…”

Preconditioning of MSCs for Acute Neurological Conditions: From Cellular to Functional Impact—A Systematic Review

“…Melatonin pretreated-AD-MSCs had higher migration to lesion site in SCI rats, presented higher differentiation into neurons, astrocytes, and oligodendrocyte lineage cells than naive AD-MSCs [56]. Nonetheless, the authors report that this strategy did not potentiate the functional improvements already observed after administration of naive MSCs to SCI rats [56]. Thus, of all the preconditioning treatments involving chemical agents, this seems to be the only strategy that was unable to promote a greater functional recovery when compared with the administration of naive MSCs.…”

“…Another preconditioning strategy that was reported to improve MSCs migration in vivo was the use of melatonin [56]. Melatonin pretreated-AD-MSCs had higher migration to lesion site in SCI rats, presented higher differentiation into neurons, astrocytes, and oligodendrocyte lineage cells than naive AD-MSCs [56]. Nonetheless, the authors report that this strategy did not potentiate the functional improvements already observed after administration of naive MSCs to SCI rats [56].…”

“…However, the authors did not evaluated the impact of this preconditioning strategy on functional outcomes of the lesioned animals. Another preconditioning strategy that was reported to improve MSCs migration in vivo was the use of melatonin [56]. Melatonin pretreated-AD-MSCs had higher migration to lesion site in SCI rats, presented higher differentiation into neurons, astrocytes, and oligodendrocyte lineage cells than naive AD-MSCs [56].…”

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

“…ADSCs are particularly interesting for their relative abundance and the ease of the isolation procedure compared to other MSC subtypes [ 19 , 145 , 146 ]. Regenerative medicine and immune-mediated disorders certainly represent the principal applications for ADSC-based strategies [ 16 , 147 , 148 , 149 , 150 , 151 , 152 ]. As well as for other MSC sources, ADSC therapeutic functions are mostly mediated by the production of extracellular vesicles and the secretion of specific soluble mediators [ 153 , 154 ].…”