title: Hemodynamic contribution of stem cell scaffolding in acute injured myocardium.
abstract: Tissue-engineered scaffolds may improve experimental outcomes in cardiac cell therapy by targeted delivery of stem cells and mechanically support an infarcted left ventricular (LV) wall. We transplanted cardiomyocyte-like cells (5×10(5)) with scaffolding via epicardial patching (cell patch, n=17) or a low-dose intramyocardial hydrogel (LD hydrogel, n=18), a high-dose (5×10(6)) intramyocardial hydrogel (HD hydrogel, n=18) or transplanting a serum-free medium control (control, n=13), a blank patch (n=14), and a blank gel (n=16) for targeted cardiomyoplasty in a myocardial infarcted rat model. LV real-time hemodynamics were assessed using a 1.9-F pressure-volume catheter 7 weeks after stem cell transplantation. All mode of scaffold transplantation protected diastolic function by preserving LV wall integrity that resulted in a lower end diastolic pressure-volume relationship (EDPVR) as compared to a control medium-injected group. Moreover, epicardial patching, but not hydrogel injection, reduced ventricular wall stress with a significantly better LV end diastolic pressure (EDP: 5.3±2.4 mmHg vs. 9.6±6.9 mmHg, p<0.05) as compared to control. Furthermore, epicardial patching additionally preserved systolic function by modulating negative remodeling through restricting dilatation of the LV chamber. In comparison to control, an improved ejection fraction in the cell patch group (80.1%±5.9% vs. 67.9%±3.2%, p<0.01) was corroborated by load-independent enhancement of the end systolic pressure-volume relationship (ESPVR: 0.88±0.61 mmHg/uL vs. 0.29±0.19 mmHg/uL, p<0.05) and preload recruitable stroke work (PRSW: 68.7±26.4 mmHg vs. 15.6±16.2 mmHg, p<0.05) in systolic function. Moreover, the cell patch group (14.2±1.7 cells/high-power field vs. 7.4±1.6 cells/high power field, p<0.05) was significantly better in myocardial retention of transplanted stem cells as compared to the LD hydrogel group. Collectively, myocardial transplantation of compliant scaffolding materials alone may physically improve wall mechanics, largely independent of stem cells. However, epicardially grafted cell patch conferred added systolic contractility by improving stem cell retention and cellular alignment leading to improved LV remodeling and geometric preservation postinfarction.
authors.affiliation: Research and Development Unit, National Heart Center Singapore, Singapore, Singapore.
authors.forename: Ling
authors.initials: L
authors.lastname: Qian
authors.forename: Winston
authors.initials: W
authors.lastname: Shim
authors.forename: Yacui
authors.initials: Y
authors.lastname: Gu
authors.forename: Mohamed
authors.initials: M
authors.lastname: Shirhan
authors.forename: Kee Pah
authors.initials: KP
authors.lastname: Lim
authors.forename: Lay Poh
authors.initials: LP
authors.lastname: Tan
authors.forename: Chong Hee
authors.initials: CH
authors.lastname: Lim
authors.forename: Yoong Kong
authors.initials: YK
authors.lastname: Sin
authors.forename: Philip
authors.initials: P
authors.lastname: Wong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology; D002452:Cell Count; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008422:Materials Testing; D055595:Mechanical Phenomena / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014463:Ultrasonography
chemical_list: D001672:Biocompatible Materials