Mesenchymal Stem Cells Provide Better Results Than Hematopoietic Precursors for the Treatment of Myocardial Infarction -- Armiñán et al. 55 (20): 2244 -- Journal of the American College of Cardiology

J Am Coll Cardiol, 2010; 55:2244-2253, doi:10.1016/j.jacc.2009.08.092
© 2010 by the American College of Cardiology Foundation

CLINICAL RESEARCH: REGENERATIVE CARDIOLOGY
Mesenchymal Stem Cells Provide Better Results Than Hematopoietic Precursors for the Treatment of Myocardial Infarction
Ana Armiñán, PhD*,, Carolina Gandía, PhD*,, J. Manuel García-Verdugo, PhD,, Elisa Lledó, PhD*,, César Trigueros, PhD, Amparo Ruiz-Saurí, MD, PhD, María Dolores Miñana, PhD||, Pilar Solves, MD, PhD¶, Rafael Payá, MD, PhD||, J. Anastasio Montero, MD, PhD*,, and Pilar Sepúlveda, PhD*,,*
* Fundación para la Investigación Hospital Universitario La Fe, Valencia, Spain
Centro de Investigación Príncipe Felipe, Valencia, Spain
Universidad de Valencia, Valencia, Spain
Fundación Inbiomed, San Sebastián, Spain
|| Hospital General Universitario de Valencia, Valencia, Spain
¶ Centro de Transfusiones de la Comunidad Valenciana, Valencia, Spain

Manuscript received July 5, 2009; revised manuscript received July 31, 2009, accepted August 10, 2009.

* Reprint requests and correspondence: Dr. Pilar Sepúlveda, Fundación para la Investigación Hospital Universitario La Fe, Regenerative Medicine and Heart Transplantation Unit, Avda Campanar 21, Valencia 46009, Spain (Email: montero_jos@gva.es).

Dr. J. Anastasio Montero, Hospital Universitario La Fe, Servicio de Cirugía Cardiaca, Avda Campanar 21, Valencia 46009, Spain (Email: pilar.sepulveda@uv.es).

Objectives: The purpose of this study was to compare the ability of human CD34+ hematopoietic stem cells and bone marrow mesenchymal stem cells (MSC) to treat myocardial infarction (MI) in a model of permanent left descendent coronary artery (LDA) ligation in nude rats.

Background: Transplantation of human CD34+ cells and MSC has been proved to be effective in treating MI, but no comparative studies have been performed to elucidate which treatment prevents left ventricular (LV) remodelling more efficiently.

Methods: Human bone marrow MSC or freshly isolated CD34+ cells from umbilical cord blood were injected intramyocardially in infarcted nude rats. Cardiac function was analyzed by echocardiography. Ventricular remodelling was evaluated by tissue histology and electron microscopy, and neo-formed vessels were quantified by immunohistochemistry. Chronic local inflammatory infiltrates were evaluated in LV wall by hematoxylin-eosin staining. Apoptosis of infarcted tissue was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay.

Results: Both cell types induced an improvement in LV cardiac function and increased tissue cell proliferation in myocardial tissue and neoangiogenesis. However, MSC were more effective for the reduction of infarct size and prevention of ventricular remodelling. Scar tissue was 17.48 ± 1.29% in the CD34 group and 10.36 ± 1.07% in the MSC group (p < 0.001 in MSC vs. CD34). Moreover, unlike MSC, CD34+-treated animals showed local inflammatory infiltrates in LV wall that persisted 4 weeks after transplantation.

Conclusions: Mesenchymal stem cells might be more effective than CD34+ cells for the healing of the infarct. This study contributes to elucidate the mechanisms by which these cell types operate in the course of MI treatment.


Key Words: hematopoietic precursors • left ventricular function • mesenchymal stem cells • myocardial infarction • paracrine factors

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Mesenchymal Stem Cells Provide Better Results Than Hematopoietic Precursors for the Treatment of Myocardial Infarction -- Armiñán et al. 55 (20): 2244 -- Journal of the American College of Cardiology