Administration of MSCs Secretome as a Therapeutic Strategy for Neonatal Hypoxic Ischemic Encephalopathy

• Autor(a) principal: Silva, Andreia Filipa Francisco Valente da
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/13897
• topic: Administração Intranasal; Células Estaminais Mesenquimais; Encefalopatia Hipóxico Isquémica; Secretoma; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

Neonatal Hypoxic-Ischemic Encephalopathy (HIE) is one of the most serious complications occurring during the perinatal period and is considered one of the leading causes of neonatal death and long-term disability. Although data differ among the literature, it is believed that about 1.5 in 1000 term births are affected in developed countries and that about 26 in 1000 births are affected in developing countries. Currently, the only therapy in clinical use for the treatment of HIE is the therapeutic hypothermia, however, it is only partially effective. Many of the emerging neuroprotective strategies that are being studied for the treatment of HIE are focused on mitigating the effects on the brain of the secondary energy failure, however, some are used in combination with therapeutic hypothermia and still present several limitations for their clinical translation. Recent studies point out mesenchymal stem cells (MSCs) as a possible therapy for HIE however, several studies have revealed limitations in their use. Moreover, it is now known that the positive impact resulting from MSCs administration is not only attributed to their migration to injured sites and differentiation but primarily to their paracrine activity. This paradigm shift towards paracrine signaling has raised interest in the potential of MSCs' conditioned medium to overcome some limitations imposed by cell therapy. Therefore, to evaluate the therapeutic potential of the intranasal administration of the secretome from umbilical cord (UC)-MSCs, a hypoxic-ischemic brain lesion was induced in rat pups and secretome administrations were performed two- and three-days post-injury. Several behavioral tests were performed in the following days to assess the impact of this strategy on cognitive and motor functions. In order to complement the results obtained, an analysis of the lesion size was carried out in all the experimental groups. Intranasal administration of UC-MSCs secretome improved sensorimotor, animal’s gait, motor coordination and recognition memory impairments observed after neonatal hypoxic-ischemic brain injury at different stages of development. However, it was not possible to draw any conclusions about its impact on spatial memory and balance impairments. Moreover, the neonatal hypoxic-ischemic injury led to a brain lesion involving about 22% of the left hemisphere that was reduced to 10% with the secretome treatment. Despite its preliminary nature, the present work has shown that secretome administration positively impacted several functional parameters known to be affected by HIE, as well as in the recovery of the volume of injured tissue. Nonetheless, more studies need to be conducted to strengthen these conclusions.