Amniotic mesenchymal cells autotransplanted in a porcine model of cardiac ischemia do not differentiate to cardiogenic phenotypes

Sartore, Saverio; Lenzi, Maddalena; Angelini, Annalisa; Chiavegato, Angela; Gasparotto, Lisa; Coppi, Paolo De; Bianco, Roberto; Gerosa, Gino
November 2005
European Journal of Cardio-Thoracic Surgery;Nov2005, Vol. 28 Issue 5, p677
Academic Journal
Abstract: Objective: Transplantation of stem cells in the acute ischemic myocardium (AMI) may play a role in the recovery of cardiac function. Here, we investigated the ability of amniotic fluid-derived mesenchymal cells (AFC) for phenotypic conversion to vascular cells and cardiomyocytes (CM) when autotransplanted in a porcine model of AMI. Methods: Single AFC preparations were taken from 12 fetuses 3 days before normal delivery. AFC were expanded in vitro and stored separately until animals of the original litter weighed 22–25kg. A new model of AMI, i.e. 45-min circumflex coronary occlusion followed by wall dissection, was used to assess AFC differentiation potential. CMFDA-labeled AFC were autogenically transplanted in the ischemic area 1 week after AMI induction. Thirty days later, pigs were sacrificed and the phenotypic profile of transplanted AFC was assessed and compared to the corresponding pre-injection pattern. Results: AFC showed in vitro to be of mesenchymal type also expressing markers of ‘embryonic stem’ cells (SSEA4 and Oct-4), as well as endothelial (von Willebrand factor, VE-cadherin) and smooth muscle (SM α-actin, SM22) cells. Thirty days after transplantation, in the survived AFC (5±1%) ‘embryonic stem’ cell markers disappeared and mesenchymal cell markers were down regulated with the exception of smooth muscle and endothelial antigens. No evidence for expression of cardiac troponin I was found.Conclusions: In the conditions used in this study, AFC were able to transdifferentiate to cells of vascular cell lineages but not to CM. Thus, porcine AFC may require further ex vivo re-programming to be suitable for therapeutic use in AMI.


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