Abstract
Resident cardiac stem cells (CSCs) represent a responsive stem cell reservoir within the adult myocardium and have a significant function in myocardial homeostasis and injury. However, the distribution, origin, homing and possible therapeutic benefits of CSCs are still under discussion. Here we investigated whether bone marrow (BM) stem cells could contribute to repopulating the pool of CSCs in heart. The engraftment of BM cells in heart was detected at a low level after BM transplantation (BMT) and ischemia/reperfusion (I/R) could increase BM cells engraftment but not significant. We clarified that more than 50% CSCs are derived from BM and confirmed that BM-derived CSCs have similar characteristics with the host CSCs. Furthermore, we transplanted BM-derived CSCs into heart ischemia models and presented evidence for the first time that BM-derived CSCs can differentiate into cardiomyocytes in vivo. In conclusions, BM stem cells could be a potential back-up source of CSCs for restoring heart function after injury or maintaining homeostasis of CSCs.
Highlights
The mammalian heart is believed to grow by enlargement but not proliferation of cardiomyocytes (CMs) during post-natal development
We confirmed the cardiomyogenic potential of bone marrow (BM) cells following syngeneic BM transplantation
We clarified that more than 50% cardiac stem cells (CSCs) are derived from BM with phase-bright culture methods and confirmed that BM-derived CSCs have similar characteristics with host CSCs
Summary
The mammalian heart is believed to grow by enlargement but not proliferation of cardiomyocytes (CMs) during post-natal development. Previous works have demonstrated that CSCs can contribute to new CMs and vascular lineages after injury[4] and improve cardiac function after CSCs injected into the infarct zone[5]. When transplanted into injured myocardium, CSCs can differentiate into functional cardiomyocytes and all the major cardiac cell lineages[8]. This rare population cells reside in specific anatomic regions of the myocardium, the so-called CSC niches, are considered both to be at the helm of the cardiac turnover and to play a fundamental role in the adaptive response of the myocardium to cardiac injury[9]. Studies have revealed that bone marrow (BM)-derived cells can improve heart function in model of myocardium ischemia[11] and hematopoietic stem cells can transdifferentiate into CMs in mouse BM transplantation (BMT) model[12,13,14]. We transplanted BM-derived CSCs into mouse heart ischemia model to investigate their therapeutic potential in vivo
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