Impact of Donor Variability in the Therapeutic Potential of Mesenchymal Stem Cells in an Animal Model of Hypoxic-Ischemic Encephalopathy

• Autor(a) principal: Araújo, Beatriz Lopes
• 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/10400.6/13876
• topic: Células Estaminais Mesenquimais; Encefalopatia Hipóxico-Isquémica; Terapia Celular; Variabilidade do Dador; Domínio/Área Científica::Engenharia e Tecnologia::Bioquímica

Hypoxic Ischemic Encephalopathy (HIE) is caused by a period of reduced blood flow to the neonatal brain and is one of the leading causes of death and severe neurological disability in the perinatal period, affecting approximately 1.5 and 2.3-26.5 per 1000 live births in developed countries and developing countries, respectively. Newborns who survive can suffer long-term neurological disabilities including cerebral palsy, epilepsy, vision and hearing loss, cognitive damage, and intellectual, behavioral, and social disorders. This neurological disorder can be caused by several factors, such as uterine rupture, placenta abruption, and prolapse of the umbilical cord. The current standard of care for this condition is therapeutic hypothermia. This method consists of reducing the body temperature or head temperature of the newborn to 33.5°C and 34.5°C, respectively, during 72h. Despite the effectiveness of this approach, it has its limitations since it has a reduced therapeutic window of application and is ineffective in severe cases. Therefore, different therapies, such as cell therapy with mesenchymal stem cells (MSCs), have been proposed. This therapy is considered safe and feasible, and several pre-clinical studies demonstrate that increases angiogenesis, neurogenesis, secretion of cytokines, neurotrophic and growth factors, decreases inflammation, and reduces the volume of the lesion. However, MSCs obtained from different donors show specific characteristics that can influence their therapeutic efficacy. To evaluate the impact of this variability on the therapeutic potential of MSCs, this study used the Rice-Vannucci model of neonatal hypoxic-ischemic injury. Two days after the lesion, a minimum effective dose of human MSCs derived from the umbilical cord of different donors was administered intravenously. To assess the impact of this strategy on the motor and cognitive function of the animals, several behavioral tests were performed at different developmental stages. The data obtained show that the functional recovery induced by the cells was significantly affected by the donor. Future studies can exploit these differences to identify markers of MSCs' therapeutic potency.