L-selectin and SDF-1 enhance the migration of mouse and human cardiac mesoangioblasts

A. Bernal, N. San Martín, M. Fernández, D. Covarello, F. Molla, A. Soldo, R. Latini, G. Cossu, B. G. Gálvez

Research output: Contribution to journalArticle

Abstract

Efficient delivery of stem cells to heart regions is still a major problem for cell therapy. Here, we report experiments aimed to improve migration of mouse and human cardiac mesoangioblasts to the damaged heart. Cardiac mesoangioblasts were induced to transmigrate through the endothelium by factors released by cardiomyocytes or cytokines, among which stromal-derived factor 1 (SDF-1) was the most potent. Cardiac mesoangioblasts were also delivered into the left ventricular (LV) chamber of mice after coronary artery ligation (CAL), and their in vivo homing to the damaged heart was found to be quite modest. Pretreatment of cardiac mesoangioblasts with SDF-1 or transient expression of L-selectin induced a two-to three-fold increase in their transmigration and homing to the damaged heart. Therefore, combined pretreatment with SDF-1 and L-selectin generated modified cardiac mesoangioblasts, 50 of which, after injection into the LV chamber of mice early after CAL, home directly to the damaged free wall of the heart. Finally, modified mouse cardiac mesoangioblasts, injected into the LV chamber regenerate a larger surface of the ventricle in long-term experiments in comparison with their control counterparts. This study defines the requirements for efficient homing of cardiac mesoangioblasts to the damaged heart and offers a new potent tool to optimize efficiency of future cell therapy protocols for cardiovascular diseases.

Original languageEnglish
Pages (from-to)345-355
Number of pages11
JournalCell Death and Differentiation
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 2012

Keywords

  • cytokines
  • homing
  • migration
  • regeneration
  • stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    Bernal, A., San Martín, N., Fernández, M., Covarello, D., Molla, F., Soldo, A., Latini, R., Cossu, G., & Gálvez, B. G. (2012). L-selectin and SDF-1 enhance the migration of mouse and human cardiac mesoangioblasts. Cell Death and Differentiation, 19(2), 345-355. https://doi.org/10.1038/cdd.2011.110