Dilated cardiomyopathy is an important cause of congestive cardiac failure in infants and children. Mobilizing hematopoietic progenitor cells is a promising intervention to this deadly disease. Aim. Evaluate granulocyte colony stimulating factor (GCSF) as therapeutic modality in children with idiopathic dilated cardiomyopathy (IDCM). Subjects and Methods. This case-control prospective study was conducted on 20 children with IDCM following up at Cardiology Clinic Children's Hospital, Ain Shams University (group 1) who were compared to another 10 age-, sex-, duration-of-illness-, and systolic-function-matched children with IDCM as control (group 2). They were subjected to history taking, clinical examination, echocardiography, and peripheral blood CD34+ cell assessment before and one week after GCSF intake for 5 consecutive days (by group 1 but not group 2). Results. A significant improvement in echocardiographic data and CD34+-T-cell increase was found in group 1 one week after GCSF intake and for the next 6 months CD34+ T cells percentage of change showed no significant correlation with the that of the left ventricular dimensions and systolic function. Conclusion. Administration of GCSF to children with IDCM resulted in clinical and echocardiographic improvement not correlated to mobilized CD34+ T cells, implying involvement of additional mechanisms over simple stem cell mobilization. 1. Introduction Dilated cardiomyopathy is an important cause of chronic congestive cardiac failure in infants and children. Although a variety of etiological factors have been listed, most patients with echocardiographically documented dilated cardiomyopathy do not possess a demonstrable cause [1]. Poor myocardial function in dilated cardiomyopathy triggers a sequence of compensatory mechanisms that favor myocardial and peripheral vascular remodeling by necrosis, fibrosis, and apoptosis which ultimately do more harm than good [2]. Medical intervention will remain the cornerstone of management until advances in surgical techniques become more widely available [3]. Mobilizing hematopoietic progenitor cells to repair the failing heart is a promising intervention to halt the progression of this deadly disease. Low doses of GCSF, five microgram per kilogram per day, were found to improve systolic function in adults with advanced systolic heart failure [2]. Bone marrow stem cells were found to contribute to the regeneration of nonhaematopoietic organs. Data from preclinical models indicate that cluster of differentiation thirty-four cells restore the microcirculation and improve
References
[1]
P. Venugopalan, A. K. Agarwal, and E. A. Worthing, “Chronic cardiac failure in children due to dilated cardiomyopathy: diagnostic approach, pathophysiology and management,” European Journal of Pediatrics, vol. 159, no. 11, pp. 803–810, 2000.
[2]
J. Joseph, P. Mehta, A. Rimawi et al., “Stem cell mobilization utilizing granulocyte colony stimulating factor in advanced chronic heart failure: lessons from a pilot study,” European Heart Journal, Supplement, vol. 10, pp. K24–K26, 2008.
[3]
W. H. Xu, J. Son, Y. Wang et al., “Granulocyte colony-stimulating factor reduces cardiomyocyte apoptosis and improves cardiac function in adriamycin-induced cardiomyopathy in rats,” Cardiovascular Drugs and Therapy, vol. 20, no. 2, pp. 85–91, 2006.
[4]
S. G. B. Furness and K. McNagny, “Beyond mere markers: functions for CD34 family of sialomucins in hematopoiesis,” Immunologic Research, vol. 34, no. 1, pp. 13–32, 2006.
[5]
P. Elliott, B. Andersson, E. Arbustini et al., “Classification of the cardiomyopathies: a position statement from the european society of cardiology working group on myocardial and pericardial diseases,” European Heart Journal, vol. 29, no. 2, pp. 270–276, 2008.
[6]
B. Brando, D. Barnett, G. Janossy et al., “Cytofluorometric methods for assessing absolute numbers of cell subsets in blood,” Communications in Clinical Cytometry, vol. 42, no. 6, pp. 327–346, 2000.
[7]
A. Abdel-Latif, R. Bolli, I. M. Tleyjeh et al., “Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis,” Archives of Internal Medicine, vol. 167, no. 10, pp. 989–997, 2007.
[8]
W. G. Harmon, L. A. Sleeper, L. Cuniberti et al., “Treating children with idiopathic dilated cardiomyopathy (from the pediatric cardiomyopathy registry),” American Journal of Cardiology, vol. 104, no. 2, pp. 281–286, 2009.
[9]
R. Olguntürk, S. Kula, G. T. Sucak, M. E. ？zdogan, D. Erer, and A. Saygili, “Peripheric stem cell transplantation in children with dilated cardiomyopathy: preliminary report of first two cases,” Pediatric Transplantation, vol. 14, no. 2, pp. 257–260, 2010.
[10]
P. J. Quesenberry, G. Colvin, and M. Abedi, “Adult stem cell plasticity: lineage potential on a continuum,” in Cardiovascular Regeneration and Stem Cell Therapy, A. Leri, P. Anversa, and W. H. Frishman, Eds., pp. 11–23, Blackwell/Futura, UK, 2007.
[11]
R. A. K. Kalil, D. Ott, R. Sant'Ana et al., “Autologous transplantation of bone marrow mononuclear stem cells by mini-thoracotomy in dilated cardiomyopathy: technique and early results,” Sao Paulo Medical Journal, vol. 126, no. 2, pp. 75–81, 2008.
[12]
S. Yamada, T. J. Nelson, R. J. Crespo-Diaz et al., “Embryonic stem cell therapy of heart failure in genetic cardiomyopathy,” Stem Cells, vol. 26, no. 10, pp. 2644–2653, 2008.
[13]
D. Zohlnh？fer, A. Dibra, T. Koppara et al., “Stem cell mobilization by granulocyte colony-stimulating factor for myocardial recovery after acute myocardial infarction. a meta-analysis,” Journal of the American College of Cardiology, vol. 51, no. 15, pp. 1429–1437, 2008.
[14]
A. Hüttmann, U. Dührsen, J. Stypmann et al., “Granulocyte colony-stimulating factor-induced blood stem cell mobilisation in patients with chronic heart failure: feasibility, safety and effects on exercise tolerance and cardiac function,” Basic Research in Cardiology, vol. 101, no. 1, pp. 78–86, 2006.
[15]
A. Kakihana, A. Ishida, M. Miyagi et al., “Improvement of cardiac function after granulocyte-colony stimulating factor-mobilized peripheral blood mononuclear cell implantation in a patient with non-ischemic dilated cardiomyopathy associated with thromboangiitis obliterans,” Internal Medicine, vol. 48, no. 12, pp. 1003–1007, 2009.
[16]
M. Harada, Y. Qin, H. Takano et al., “G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes,” Nature Medicine, vol. 11, no. 3, pp. 305–311, 2005.
[17]
S. Dimmeler, J. Burchfield, and A. M. Zeiher, “Cell-based therapy of myocardial infarction,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 2, pp. 208–216, 2008.
