An important issue in need of resolution concerns whether myocyte regeneration in the adult heart is controlled exclusively by activation and commitment of resident c-kit-positive cardiac stem cells (CSCs), or circulating hematopoietic stem cells (HSCs) from the bone marrow contribute to cardiomyogenesis. Although CSCs divide asymmetrically being able to self-renew and form a specialized progeny, whether this stem cell compartment is fully independent from the pool of HSCs in regulating cardiac homeostasis remains controversial. In an attempt to resolve this biological problem, bone marrow transplantation and a model of parabiosis will be employed to establish quantitatively the relative role of HSCs and CSCs in myocyte renewal in adulthood and in tissue regeneration following ischemic myocardial injury. An additional complementary question is whether stem cells in the niches are all of cardiac origin or HSCs migrate from the bone marrow to the myocardial niches where they attain a new identity participating in the turnover of these primitive cells in their microenvironment. If this were the case, HSCs would be involved in the preservation of the stem cell pool in the heart, which constitutes the growth reserve of the myocardium throughout the course of life. A common mechanism involving oscillations in intracellular Ca2+, cell cycle entry, asymmetric division, and nuclear shuttling of the myocyte transcription factor Nkx2.5 is postulated to regulate the lineage specification of CSCs and HSCs into cardiomyocytes. Ultimately, the molecular mechanisms of HSC transdifferentiation will be identified and the involvement of the bone marrow in cardiomyogenesis carefully defined.
This research aims at the identification and quantification of the celular proceses that regulate cardiac homeostasis and myocardial regeneration following ischemic injury. Both CSCs and HSCs are postulated to contribute to myocyte regeneration physiologically and after myocardial infarction. If successful, novel strategies for the treatment f the diseased heart may be identified.
| Borghetti, Giulia; Eisenberg, Carol A; Signore, Sergio et al. (2018) Notch signaling modulates the electrical behavior of cardiomyocytes. Am J Physiol Heart Circ Physiol 314:H68-H81 |
| Meo, Marianna; Meste, Olivier; Signore, Sergio et al. (2016) Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm. J Am Heart Assoc 5: |
| Sorrentino, Andrea; Signore, Sergio; Qanud, Khaled et al. (2016) Myocyte repolarization modulates myocardial function in aging dogs. Am J Physiol Heart Circ Physiol 310:H873-90 |
| Signore, Sergio; Sorrentino, Andrea; Borghetti, Giulia et al. (2015) Late Na(+) current and protracted electrical recovery are critical determinants of the aging myopathy. Nat Commun 6:8803 |
| Leri, Annarosa; Rota, Marcello; Pasqualini, Francesco S et al. (2015) Origin of cardiomyocytes in the adult heart. Circ Res 116:150-66 |
| Goichberg, Polina; Chang, Jerway; Liao, Ronglih et al. (2014) Cardiac stem cells: biology and clinical applications. Antioxid Redox Signal 21:2002-17 |
| D'Amario, Domenico; Leone, Antonio M; Iaconelli, Antonio et al. (2014) Growth properties of cardiac stem cells are a novel biomarker of patients' outcome after coronary bypass surgery. Circulation 129:157-72 |
| Leri, Annarosa; Rota, Marcello; Hosoda, Toru et al. (2014) Cardiac stem cell niches. Stem Cell Res 13:631-46 |
| Sanada, Fumihiro; Kim, Junghyun; Czarna, Anna et al. (2014) c-Kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy. Circ Res 114:41-55 |
| Rota, Marcello; Leri, Annarosa; Anversa, Piero (2014) Human heart failure: is cell therapy a valid option? Biochem Pharmacol 88:129-38 |
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