Abstract
Recent studies have revealed the existence of multipotent nestin‐immunoreactive cells in the adult mammalian heart. These cells were recruited to infarct site following ischemic injury and differentiated to a vascular lineage leading to de novo blood vessel formation. Here, we show that a sub‐population of cardiac resident nestin^(+)^ cells can further differentiate to a neuronal‐like fate in vivo following myocardial infarction. In the ischemically damaged rat heart, neurofilament‐M^(+)^ fibres were detected innervating the peri‐infarct/infarct region and the preponderance of these fibres were physically associated with processes emanating from nestin^(+)^ cells. One week after isogenic heterotopic cardiac transplantation, the beating transplanted rat heart was devoid of neurofilament‐M^(+)^ fibre staining. The superimposition of an ischemic insult to the transplanted heart led to the de novo synthesis of neurofilament‐M^(+)^ fibres by cardiac resident nestin^(+)^ cells. Nerve growth factor infusion and the exposure of normal rats to intermittent hypoxia significantly increased the density of neurofilament‐M^(+)^ fibres in the heart. However, these newly formed neurofilament‐M^(+)^ fibres were not physically associated with nestin^(+)^ processes. These data highlight a novel paradigm of reparative fibrosis as a subpopulation of cardiac resident nestin^(+)^ cells directly contributed to neural remodelling of the peri‐infarct/infarct region of the ischemically damaged rat heart via the de novo synthesis of neurofilament‐M fibres. J. Cell. Physiol. 226: 1157–1165, 2011. © 2010 Wiley‐Liss, Inc.