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Introduction
Acute myocardial infarction (AMI) remains a major cause of chronic heart failure (HF) due to a loss of myocardial tissue. Although AMI has been postulated to lead to an irrecoverable loss of cardiomyocytes, bone marrow-derived cells (BMCs) might be able to differentiate into cardiomyocytes after AMI. Several experimental studies have confirmed this cardiomyocytogenic capability of BMCs (1–3), whereas others have excluded the differentiation of BMCs in cardiomyocytes (4–8). Clinical trials have demonstrated beneficial effects of BMC treatment (9–11) after AMI with improved functional parameters (9–11) or a complete absence of effects (12). A recent meta-analysis brought the therapeutic impact of BMCs into question (13). Given these controversial experimental and clinical results, the differential potential of BMCs has been critically challenged and the (patho-)physiological relevance of BMCs in the repair of myocardial damage remains unclear. In order to gain a better understanding of the role of BMCs during pathophysiological processes, improving our knowledge of the physiological role of BMCs in the myocardium is indispensible. Thus, we examined the role of BMCs in the physiological aging processes of the heart. For this purpose, we used a mouse model in which the original bone marrow was replaced by an enhanced green fluorescent protein (eGFP)-marked stem cell pool. These labeled cells offer a possibility of clearly identifying the fate and behavior of potentially differentiated BMC offspring.
Materials and methods
Bone marrow transplantation and transgenic mice
Bone marrow transplantation (BMTx) was performed according to a previously described protocol (6). Briefly, C57BL/6-TgN(ACTbEGFP)1Osb transgenic mice (Jackson Laboratory, Bar Harbor, ME, USA) served as bone marrow donors. In this transgenic line, all cells, with the exception of erythrocytes and hair follicle cells, express eGFP and appear green in the presence of excitation wavelengths (14). A total of 36 mice were transplanted. The success of BMTx was monitored by flow cytometric analysis (FACSCalibur, BD Biosciences, Germany).
In 18 mice, hearts were excised at the age of 4 months to serve as the young control group (group A). To investigate the aging myocardium, 18 mice were euthanized at the age of 18 months (group B).
All investigations conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication no. 85-23, revised 1996) and...