The homing of bone marrow stem cells is differentially activated in ischemic and valvular heart\xa0diseases and influenced by beta-blockers

Melissa Kristocheck,Carine Ghem,Renato A K Kalil,Lucinara D Dias,Bruna Eibel,Melissa M Markoski

doi:10.1186/s12967-018-1520-9

Abstract

BackgroundCell homing is the mechanism by which an injury releases signaling molecules that cause recruitment, proliferation, migration and differentiation of progenitor cells. Stromal derived factor-1 (SDF-1) and its receptor CXCR4 are key molecules involved in homing and little is known about their activation in cardiopathies. Here, we assessed the homing activation status of bone marrow cells (BMC) concerning the SDF-1 and CXCR4 expression in ischemic (IHD) and valvular (VHD) heart diseases.MethodsThe SDF-1 and inflammatory profile were analyzed by ELISA from plasma obtained bone marrow of ischemic heart patients (IHD, n = 41), valvular heart patients (VHD, n = 30) and healthy controls (C, n = 9). Flow cytometry was used to evaluate CXCR4 (CD184) expression on the surface of bone marrow cells, and the CXCR4 expression was estimated by real-time quantitative PCR.ResultsThe SDF-1 levels in the groups IHD, VHD and control were, respectively, 230, 530 and 620 pg/mL (P = 0.483), and was decreased in VHD patients using beta-blockers (263 pg/mL) when compared with other (844 pg/mL) (P = 0.023). Compared with IHD, the VHD group showed higher CXCR4 (P = 0.071) and CXCR7 (P = 0.082) mRNA expression although no difference in the level of CXCR4+ bone marrow cells was found between groups (P = 0.360).ConclusionIn conclusion, pathophysiological differences between IHD and VHD can affect the molecules involved in the activation of homing. In addition, the use of beta-blockers appears to interfere in this mechanism, a fact that should be considered in protocols that use BMC.

Highlights

Cell homing is the mechanism by which an injury releases signaling molecules that cause recruitment, proliferation, migration and differentiation of progenitor cells
CXCR4+ cells are present in same levels in the bone marrow of ischemic heart disease (IHD) and valvular heart disease (VHD) patients The presence of CXCR4+ cells (CD184+) in the population of bone marrow cells (BMC) in the groups of patients was investigated using flow cytometry
Considering the importance of stem cell homing to the cardiomyoplasty outcome [6], this study analyzed its activation status through the expression of key molecules involved in this mechanism, the chemokine Stromal derived factor-1 (SDF-1) and its receptor CXCR4 in BM samples of patients with ischemic and valvular heart diseases

Summary

Introduction

Cell homing is the mechanism by which an injury releases signaling molecules that cause recruitment, proliferation, migration and differentiation of progenitor cells. Stromal derived factor-1 (SDF-1) and its receptor CXCR4 are key molecules involved in homing and little is known about their activation in cardiopathies. We assessed the homing activation status of bone marrow cells (BMC) concerning the SDF-1 and CXCR4 expression in ischemic (IHD) and valvular (VHD) heart diseases. Most studies have focused on the use of bone marrow-derived cells (BMC) in groups of patients with different heart diseases, describing a modest improvement in cardiac parameters, Kristocheck et al J Transl Med (2018) 16:133 quality of life and patients’ symptoms [4]. Despite the well-designed, promising clinical studies, the mechanisms and molecules involved in cardiac repair and other issues that may optimize the beneficial effects of cardiomyoplasty remain to be clarified

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