Bone Marrow-Derived Progenitor Cells Are Functionally Impaired in Ischemic Heart Disease

J Cardiovasc Transl Res. 2016 Aug;9(4):266-78. doi: 10.1007/s12265-016-9707-z. Epub 2016 Jul 25.

Abstract

To determine whether the presence of ischemic heart disease (IHD) per se, or rather the co-presence of heart failure (HF), is the primum movens for less effective stem cell products in autologous stem cell therapy, we assessed numbers and function of bone marrow (BM)-derived progenitor cells in patients with coronary artery disease (n = 17), HF due to ischemic cardiomyopathy (n = 8), non-ischemic HF (n = 7), and control subjects (n = 11). Myeloid and erythroid differentiation capacity of BM-derived mononuclear cells was impaired in patients with underlying IHD but not with non-ischemic HF. Migration capacity decreased with increasing IHD severity. Hence, IHD, with or without associated cardiomyopathy, is an important determinant of progenitor cell function. No depletion of hematopoietic and endothelial progenitor cells (EPC) within the BM was observed, while circulating EPC numbers were increased in the presence of IHD, suggesting active recruitment. The observed myelosuppression was not driven by inflammation and thus other mechanisms are at play.

Keywords: Bone marrow; Heart failure; Inflammation; Ischemic heart disease; Progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alkaline Phosphatase / metabolism
  • Angiogenic Proteins / genetics
  • Angiogenic Proteins / metabolism
  • Biomarkers / blood
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology*
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / pathology*
  • Case-Control Studies
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Endothelial Progenitor Cells / metabolism
  • Endothelial Progenitor Cells / pathology*
  • Female
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Inflammation Mediators / metabolism
  • Male
  • Middle Aged
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / pathology*
  • Phenotype
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism

Substances

  • Angiogenic Proteins
  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Receptors, Cytokine
  • Alkaline Phosphatase