Shopping cart
Soluble factors from multipotent mesenchymal stromal cells have antinecrotic effect on cardiomyocytes in vitro and improve cardiac function in infarcted rat hearts
Authors: P. Fidelis-de-Oliveira, J.P.S. Werneck-de-Castro, V. Pinho-Ribeiro, B.C.M. Shalom, J.A. Nascimento-Silva, R.H. Costa e Souza, I.S. Cruz, R.R. Rangel, R.C.S. Goldenberg, A.C. Campos-de-Carvalho
Source: Cell Transplantation
Publisher: Cognizant Communication Corporation
Buy & download fulltext article:
The full text is free.
View now:
Abstract:
The mechanisms underlying the functional improvement after injection of multipotent mesenchymal stromal cells (MSCs) in infarcted hearts remain incompletely understood. The aim of this study was to investigate if soluble factors secreted by MSCs promote cardioprotection. For this purpose, conditioned medium (CM) was obtained after three passages from MSC cultures submitted to 72 hours of conditioning in serum-free DMEM under normoxia (NCM) or hypoxia (HCM). CM was concentrated 25-fold before use (NCM-25X, concentrated normoxia conditioned medium; HCM-25X ‒ concentrated hypoxia conditioned medium). The in vitro cardioprotection was evaluated in neonatal ventricular cardiomyocytes by quantifying apoptosis after 24 hours of serum deprivation associated with hypoxia (1% O ₂) in absence or presence of NCM and HCM (non-concentrated and 25-fold concentrated). The in vivo cardioprotection of HCM was tested in a model of myocardial infarction (MI) induced in Wistar male rats by permanent left coronary occlusion. Intramyocardial injection of HCM-25X (n=14) or non-conditioned DMEM (n=16) was performed 3 hours after coronary occlusion and cardiac function was evaluated 19-21 days after medium injection. Cardiac function was evaluated by electro and echocardiogram, left ventricular catheterization and treadmill test. The in vitro results showed that HCM was able to decrease cardiomyocyte necrosis. The in vivo results showed that HCM-25X administrated 3 hours after AMI was able to promote a significant reduction (35%) in left ventricular end-diastolic pressure and improvement of cardiac contractility (15%) and relaxation (12%). These results suggest that soluble factors released in vitro by MSCs are able to promote cardioprotection in vitro and improve cardiac function in vivo.Document Type:
DOI: http://dx.doi.org/10.3727/096368911X623916
Appeared or available online: February 2, 2012
Key
Print this page