Abstract
It is now recognized that transplantation of bone marrow cells (BMCs) into infarcted hearts has the capacity to improve the cardiac function through paracrine effects. However, detailed expression levels of paracrine factors in BMCs in infarcted hearts are poorly described. By use of laser capture microdissection combined with real-time PCR, we depicted the expression profiles of paracrine factors in infarcted hearts versus normal hearts. Consistent with the in vivo observation, a similar expression pattern was evidenced in cultured BMCs. Furthermore, BMCs displayed heterogeneity of paracrine effects in infarcted hearts as analyzed at the single cell level using single cell PCR. Interestingly, the CD45+ subpopulation showed higher expression levels of angiogenic factors compared to other subpopulations. Finally, most angiogenic factors were induced under the microenvironment of infarction. Our study demonstrated the heterogeneity of paracrine effects in BMCs at single cell level in infarcted hearts, highlighting preferential expression of angiogenic factors in the CD45+ subpopulation. These findings broaden our understanding of paracrine effects of BMCs in vivo, and offer new insights into BMCs therapy in myocardial infarction (MI).
Highlights
Despite advances in our understanding and treatment of coronary artery disease, myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide
For the first time to our knowledge, delineated the regulation of paracrine factors released by bone marrow cells (BMCs) in vivo, uncovered the heterogeneity of paracrine effects of BMCs at a single cell level in infarcted hearts, and revealed preferential secretion of angiogenic factors in the CD45+ subpopulation in ischemic myocardium
By use of GFP transgenic mice and Laser Capture Microdissection (LCM), we had the unique opportunity to monitor the expression of various paracrine factors in vivo, and showed that BMCs expressed a broad spectrum of paracrine factors in infarcted hearts
Summary
Despite advances in our understanding and treatment of coronary artery disease, myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide. In order to ensure the safety and effectiveness of BMC therapy, extensive studies were performed to dissect the mechanisms underlying their therapeutic actions. Transdifferentiation into cardiomyocytes and vascular lineage cells has been originally proposed as the principal mechanism accounting for improved cardiac function. Other groups failed to detect cardiac transdifferentiation in hearts transplanted with BMCs derived hematopoietic stem cells (HSCs) [10,11]. Given the ongoing scientific debates, a different hypothesis has been raised, emphasizing paracrine effects of stem cells in the treatment of MI [12]. Takahashi et al injected conditioned medium from bone marrow derived mononuclear cells (BM-MNCs) into infarcted hearts and observed an overall improvement of cardiac function [13]. Given that BMCs are composed of different cell populations, analyses of the paracrine effects that distinguish the different subpopulations were rarely reported
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