title: Global contractility increment in nonischemic dilated cardiomyopathy after free wall-only intramyocardial injection of autologous bone marrow mononuclear cells: an insight over stem cells clinical mechanism of action.
abstract: Bone marrow mononuclear cells (BMMC) effects have been investigated in small series of nonischemic dilated cardiomyopathy (NIDC). Left ventricular myocardial contractility improvements occur, but doubt remains about their mechanism of action. We compared contractility changes in areas treated (free wall) and nontreated (septal wall) with BMMC, in selected patients who have showed significant ventricular improvement after free wall-only intramyocardial stem cells injection. From 15 patients with functional class III/IV (NYHA) and LVEF inferior to 35%, who received 9.6 ± 2.6 × 10(7) BMMC divided into 10 points over the left ventricular free wall, 7 (46.7%) showed LVEF relative improvement greater than 15%. Those patients were selected for further contractility study. BMMC were collected from iliac bone and isolated with Ficoll-Hypaque. Magnetic resonance imaging was used to measure the systolic thickening of the septal (nontreated) and free wall (treated) before injection and 3 months postoperatively. Mean systolic septal wall thickening increased from 0.46 to 1.23 mm (an absolute 0.77 ± 1.3 mm and relative 167.4% increase) and in the free wall from 1.13 to 1.87 mm (an absolute 0.74 ± 1.5 mm and relative increase of 65.5%). There was no difference in the rate of absolute or relative systolic thickening between the two walls (p = 0.866 and 1.0, respectively), when cells were injected only in the left ventricular free wall. BMMC transplantation in nonischemic dilated cardiomyopathy can improve ventricular function by an overall effect, even in areas that are not directly injected. This finding favors the existence of a diffuse mechanism of action, rather than a local effect, and should be reminded when the pathophysiology of stem cells is considered.
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul/FUC, Porto Alegre, RS, Brazil.
authors.forename: Roberto T
authors.initials: RT
authors.lastname: Sant'anna
authors.forename: Renato A K
authors.initials: RA
authors.lastname: Kalil
authors.forename: Angelo S
authors.initials: AS
authors.lastname: Pretto Neto
authors.forename: Fernando
authors.initials: F
authors.lastname: Pivatto Júnior
authors.forename: James
authors.initials: J
authors.lastname: Fracasso
authors.forename: João R M
authors.initials: JR
authors.lastname: Sant'anna
authors.forename: Maurício
authors.initials: M
authors.lastname: Marques
authors.forename: Melissa
authors.initials: M
authors.lastname: Markoski
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Prates
authors.forename: Nance B
authors.initials: NB
authors.lastname: Nardi
authors.forename: Ivo A
authors.initials: IA
authors.lastname: Nesralla
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000628:therapy*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D011877:Radionuclide Imaging; D033581:Stem Cell Transplantation; D013997:Time Factors; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left