title: Cord lining-mesenchymal stem cells graft supplemented with an omental flap induces myocardial revascularization and ameliorates cardiac dysfunction in a rat model of chronic ischemic heart failure.
abstract: Myocardial restoration using tissue-engineered grafts to regenerate the ischemic myocardium offers improved donor cell retention, yet a limited cell survival resulting from poor vascularization needs to be addressed. A cell type derived from the subamnion, namely, cord-lining mesenchymal stem cells (CL-MSC), has recently been identified. Here we present a restorative strategy that combines a fibrin graft containing human CL-MSC and omental flap providing, thereby, cell-, structural-, and angiogenic support to the injured myocardium. The graft consisted of a mixture of 2×10(6) CL-MSC-GFP-Fluc and fibrin. Myocardial infarction (MI) was induced in nude rats and following confirmation of ensued heart failure with echocardiography 2 weeks after injury, therapeutic intervention was performed as follows: untreated (MI, n=7), CL-MSC graft (CL-MSCG, n=8), CL-MSCG and omental flap (CL-MSCG+OM, n=11), and omental flap (OM, n=8). In vivo bioluminescence imaging at 1, 3, 7, and 14 days post-treatment indicated comparable early donor cell viability between the CL-MSCG and CL-MSCG+OM. Treatment with CL-MSCG+OM improved the myocardial function as assessed by the measurement of end-diastolic left ventricular (LV) pressure (3.53±0.34 vs. 5.21±0.54 mmHg, p<0.05), contractility (+dP/dt, 3383.8±250.78 mmHg vs. 2464.9±191.8 mmHg, p<0.05), and the relaxation rate (-dP/dt, -2707.2±250.7 mmHg vs. 1948.7±207.8 mmHg, p<0.05), compared to MI control 6 weeks after ischemic injury. Furthermore, evidence of a 20.32% increase in the ejection fraction was observed in CL-MSCG+OM rats from week 2 to 6 after injury. Both CL-MSCG and CL-MSCG+OM led to an enhanced cardiac output (p<0.05), and attenuated the infarct size (35.7%±4.2% and 34.7%±4.8%), as compared to MI (60.7%±3.1%; p<0.01 and p<0.001, respectively). All treated groups had a higher arteriole density than controls. Yet, a higher amount of functional blood vessels, and a 20-fold increase in arteriole numbers were found in CL-MSCG+OM. Altogether, CL-MSCGs supplemented with vascular supply have the potential to repair the failing, chronically ischemic heart by improving myocardial revascularization, attenuating remodeling, and ameliorating cardiac dysfunction.
authors: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors: Shera
authors: S
authors: Lilyanna
authors: Eliana C
authors: EC
authors: Martinez
authors: Thang D
authors: TD
authors: Vu
authors: Lieng H
authors: LH
authors: Ling
authors: Shu U
authors: SU
authors: Gan
authors: Ai L
authors: AL
authors: Tan
authors: Thang T
authors: TT
authors: Phan
authors: Theo
authors: T
authors: Kofidis
mesh_terms: D000818:Animals; D002470:Cell Survival; D002908:Chronic Disease; D004195:Disease Models, Animal; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D018613:Microscopy, Confocal; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009204:Myocardial Revascularization; D009852:Omentum / Q000601:surgery*; D010641:Phenotype; D051381:Rats; D013524:Surgical Flaps; D014463:Ultrasonography; D014470:Umbilical Cord / Q000166:cytology*; D016277:Ventricular Function, Left