Evaluation of stem cell therapy on cardiac function and exercise capacity in rats with aortic insufficiency

• Grant number: 19/02024-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2019
• End date: June 30, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Patrícia Fidelis de Oliveira
• Grantee: Ronny Peterson Cabral Filho
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Aortic insufficiency (AoI) represents a condition of volumetric overload caused by valve incompetence in its closure. The differentiation of stem cells (SC) in the host tissue is not confirmed in vivo and other mechanisms such as cytoprotection and antifibrotic effects have been suggested which increases the use of SC in cardiac diseases without significant myocytes loss as in AoI. Therefore, the present study aims to investigate whether therapy with bone marrow stromal mesenchymal cells (MSC, an SC enriched portion) promotes morphofunctional cardiac improvement at rest and increases exercise capacity in rats with AoI. MSCs will be obtained from the bone marrow of a donor rat and then characterized by immunophenotyping and osteogenic and adipogenic differentiation in vitro. The MSCs will be expanded for in vivo administration. The AoI will be surgically induced in Wistar rats and will be confirmed after one week by echocardiography (ECHO). False-operated animals (SHAM) will be normalcy control. After one week of AoI, intramyocardial injection (i.m, 100 uL) will be given constituting the groups: SHAM; AoI+DMEM (cell-free culture medium injection) and AoI+MSC (10e6 cells/100uL). The posttreatment ECHO assessments will be made on the 4th and 8th week after IAo. At the 8th week, cardiac function will be evaluated by means of the treadmill test, blood pressure (autonomic tonus analysis, baroreflex sensitivity and heart rate variability) and left ventricular pressure recordings. The animals will be killed and the hearts removed for fibrosis quantification. The results of this project may motivate future studies investigating the therapeutic application of MSC in AoI as an alternative or adjuvant therapy to valve prosthesis surgery.