title: Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium.
abstract: OBJECTIVE
  To determine the optimal bone marrow (BM) cell types, and their potential mechanisms of action for neovascularization in chronic ischaemic myocardium.
  
  
  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 dP/dt (+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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. hftse@hkucc.hku.hk
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Zhu
authors.forename: Liao
authors.initials: L
authors.lastname: Songyan
authors.forename: Qing-Yong
authors.initials: QY
authors.lastname: Zhang
authors.forename: Wing-Hon
authors.initials: WH
authors.lastname: Lai
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
authors.forename: John
authors.initials: J
authors.lastname: Nicholls
authors.forename: Chu-Pak
authors.initials: CP
authors.lastname: Lau
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000502:physiology*; D002452:Cell Count; D002454:Cell Differentiation; D002908:Chronic Disease; D022062:Electrophysiologic Techniques, Cardiac; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008863:Microspheres; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009204:Myocardial Revascularization / Q000379:methods*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D013234:Stem Cells / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016277:Ventricular Function, Left
chemical_list: D042461:Vascular Endothelial Growth Factor A