Cellular therapies in a stroke model

• Grant number: 24/18319-8
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: January 02, 2025
• End date: February 11, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Rosalia Mendez-Otero
• Grantee: Micaela Giovana Alves Pinheiro da Cunha
• Host Institution: Instituto de Biofísica Carlos Chagas Filho (IBCCF). Universidade Federal do Rio de Janeiro (UFRJ). Ministério da Educação (Brasil)

Abstract

Stroke is the second leading cause of death and the third leading cause of death and disability combined globally, and can be divided into ischemic or hemorrhagic. In Brazil, since 2019, stroke has surpassed heart attack as the leading cause of death in the country, and its incidence ranges from 54.3 to 77 per 100,000 inhabitants, with 50,133 deaths recorded until August 2024. The accumulation of blood in the brain parenchyma causes primary damage due to the mass effect and secondary damage through pathological pathways such as cytotoxicity, oxidative stress and inflammation. This results in the rupture of the blood-brain barrier, cerebral edema and massive cell death. Current treatment options for hemorrhagic stroke are limited, consisting mainly of cranial decompression surgery, indicated in specific cases, blood pressure control and life support measures. However, these approaches do not directly act on the secondary lesion caused by stroke, highlighting the urgent need for therapies that modulate the inflammatory response. In this context, cell therapy, especially with mesenchymal stem cells (MSCs), appears to be a promising alternative. Thus, this project aims to explore the mechanisms of action and establish the in vivo proof of concept of treatment with hWJ-MSCs in the acute phase of stroke, aiming at translation into clinical practice. To this end, the trainee will receive theoretical and practical training in a surgical model of stroke induction, functional testing using a neurological scale, as well as histological and immunohistochemical analysis, in order to determine the effects of hWJ-MSCs administration in preclinical models of stroke. The approach that the trainee will develop with our research group offers an innovative solution to accelerate the discovery of potential translational therapies, exploring the mechanisms of action of Wharton's jelly mesenchymal stem cells (hWJ-MSCs) in the treatment of the acute phase of hemorrhagic stroke, with an emphasis on modulating the inflammatory response and neuronal protection. This strategy can be easily adapted and applied to studies of other cerebrovascular diseases besides stroke. (AU)