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

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12265-016-9707-z) contains supplementary material, which is available to authorized users.

Identification of a CTRP9 C-Terminal polypeptide capable of enhancing bone-derived mesenchymal stem cell cardioprotection through promoting angiogenic exosome production

“…Recent studies demonstrate these factors may cluster into extracellular vesicles, particularly exosomes, which transfer proteins, microRNAs, and lipids to cardiomyocytes, mediating cardioprotection [ 33 , 34 ]. Unfortunately, the reparative capacity of mesenchymal stem cells significantly declines post-MI, as these cells from post-MI patients possess decreased cardioprotective capability [ [35] , [36] , [37] ]. Strategies capable of improving the reparative secretome will restore mesenchymal stem cell cardioreparative capability.…”

Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis

“…Another option for using senolytics may with the goal of improving outcomes of autologous transplantation therapies of bone marrow-derived angiogenic cells in ischaemic heart failure. In ischaemic heart failure patients, these cells are severely impaired 186 , 187 and display markers of senescence, 188 , 189 disabling their use for patient-derived cellular therapy. Senolytics may be used to remove senescent cells, either in vivo or ex vivo , leading to a rejuvenated population and more effective therapeutic outcomes.…”

Comparative Preliminary Analysis of Umbilical Cord Blood-, Healthy Adult Peripheral Blood- and Myocardial Infarct Peripheral Blood-Derived Endothelial Progenitor Cells

“…In other words, no significant differences were identified between CB-EPC, PB-EPC, and MI-EPC either in endothelial functional assays such as endothelial tube formation and Ac-LDL uptake or in the expression of surface markers (CD34, CD133, CD45, and VWF). The differentiation capacity of progenitor cells is reduced in heart disease patients, which may hamper the clinical efficacy of autologous stem cell therapy; progenitor cells from outside patient body should be added to increase the success rate of cell therapy [25].…”