Premium
Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium
Author(s) -
Tse HungFat,
Siu ChungWah,
Zhu ShuGuang,
Songyan Liao,
Zhang QingYong,
Lai WingHon,
Kwong YokLam,
Nicholls John,
Lau ChuPak
Publication year - 2007
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2007.03.008
Subject(s) - medicine , neovascularization , endocardium , bone marrow , angiogenesis , perfusion , saline , cardiology , cd31 , vascular endothelial growth factor , arteriogenesis , vegf receptors
Objective To determine the optimal bone marrow (BM) cell types, and their potential mechanisms of action for neovascularization in chronic ischaemic myocardium. Methods and results The functional effects, angiogenic potential and cytokine expression of direct intramyocardial implantation of autologous BM CD31‐positive endothelial progenitor cells (EPC, n =9), BM mononuclear cells (MNCs, n =9), and saline ( n =9) were compared in a swine model of chronic ischaemic myocardium. Autologous BM cells were harvested and catheter‐based electromechanical mapping‐guided direct intramyocardial injection was performed to target ischaemic myocardium. After 12 weeks, injection of BM‐MNC resulted in significant improvements in left ventricular d P /d t (+21±8%, P =0.032), left ventricular pressure (+17±4%, P =0.048) and regional microsphere myocardial perfusion over ischaemic endocardium (+74±28%, P <0.05) and epicardium (+73±29%, P <0.05). No significant effects were observed following injection of BM‐EPC or saline. Capillary density (1132±69 versus 903±44 per mm 2 , P =0.047) and expression of mRNA of vascular endothelial growth factor (VEGF, 32.3±5.6 versus 13.1±3.7, P <0.05,) and angiopoietin‐2 (23.9±3.6 versus 13.7±3.1, P <0.05) in ischaemic myocardium was significantly greater in the BM‐MNC group than the saline group. The capillary density in ischaemic myocardium demonstrated a significant positive correlation with VEGF expression ( r =0.61, P <0.001). Conclusion Catheter‐based direct intramyocardial injection of BM‐MNC enhanced angiogenesis more effectively than BM‐EPC or saline, possibly via a paracrine effect, with increased expression of VEGF that subsequently improved cardiac performance of ischaemic myocardium.