Mesenchymal Stem Cells Protect Cardiomyocytes

Abstract

Possible therapeutic benefits of stem cell treatments have been widely investigated recently. We have presented initial reports that co-culturing mesenchymal stem cells (MSC, Lonza) with rat heart cells in primary culture can prevent the consequences of the treatment with a inflammatory bacterial endotoxin (LPS, Lipopolysaccharide-A). We now investigate how the MSC produce their beneficial actions. Using sparse primary cultures of neonatal rat ventricular or adult rat ventricular myocytes with either MSC or control cells (fibroblasts), we examine cardiac Ca2+ signaling. LPS causes Ca2+ signaling anomalies which include delayed afterdepolarizations (DADs) and Ca2+-enhanced early afterdepolarizations (EADs). We find that co-cultures with cells co-mingled can prevent the untowards actions of LPS on the cardiac myocytes. The negative consequences of LPS are alterations in the normal [Ca2+]i transient that is stimulated by field shocks as described above. Since the benefit of MSC co-culture are found even when a solute permeable / cell impermeant membrane separates the MSC from the LPS treated cardiac myocytes, we conclude that a paracrine action of the MSC can account for the treatment attributed to the MSCs. We continue to investigate possible beneficial signaling pathways that may explain the paracrine effect of MSCs.View Large Image | View Hi-Res Image | Download PowerPoint Slide