title: iPSC-derived human cardiac progenitor cells improve ventricular remodelling via angiogenesis and interstitial networking of infarcted myocardium.
abstract: We investigate the effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived progenitors and cardiomyocytes into acutely infarcted myocardium in severe combined immune deficiency mice. A total of 2 × 10(5) progenitors, cardiomyocytes or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Myocardial function was assessed at 2-week and 4-week post-infarction by using echocardiography and pressure-volume catheterization. Early myocardial remodelling was observed at 2-week with echocardiography derived stroke volume (SV) in saline (20.45 ± 7.36 μl, P < 0.05) and cardiomyocyte (19.52 ± 3.97 μl, P < 0.05) groups, but not in progenitor group (25.65 ± 3.61 μl), significantly deteriorated as compared to sham control group (28.41 ± 4.41 μl). Consistently, pressure-volume haemodynamic measurements showed worsening chamber dilation in saline (EDV: 23.24 ± 5.01 μl, P < 0.05; ESV: 17.08 ± 5.82 μl, P < 0.05) and cardiomyocyte (EDV: 26.45 ± 5.69 μl, P < 0.05; ESV: 18.03 ± 6.58 μl, P < 0.05) groups by 4-week post-infarction as compared to control (EDV: 15.26 ± 2.96 μl; ESV: 8.41 ± 2.94 μl). In contrast, cardiac progenitors (EDV: 20.09 ± 7.76 μl; ESV: 13.98 ± 6.74 μl) persistently protected chamber geometry against negative cardiac remodelling. Similarly, as compared to sham control (54.64 ± 11.37%), LV ejection fraction was preserved in progenitor group from 2-(38.68 ± 7.34%) to 4-week (39.56 ± 13.26%) while cardiomyocyte (36.52 ± 11.39%, P < 0.05) and saline (35.34 ± 11.86%, P < 0.05) groups deteriorated early at 2-week. Improvements of myocardial function in the progenitor group corresponded to increased vascularization (16.12 ± 1.49/mm(2) to 25.48 ± 2.08/mm(2) myocardial tissue, P < 0.05) and coincided with augmented networking of cardiac telocytes in the interstitial space of infarcted zone.
authors.affiliation: National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
authors.forename: K P Myu Mia
authors.initials: KP
authors.lastname: Ja
authors.affiliation: National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.|Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Miao
authors.affiliation: National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
authors.forename: Nicole Gui
authors.initials: NG
authors.lastname: Zhen Tee
authors.affiliation: National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
authors.forename: Sze Yun
authors.initials: SY
authors.lastname: Lim
authors.affiliation: National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
authors.forename: Manasi
authors.initials: M
authors.lastname: Nandihalli
authors.affiliation: National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
authors.forename: Chrishan J A
authors.initials: CJA
authors.lastname: Ramachandra
authors.affiliation: National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.|DUKE-NUS Graduate Medical School.
authors.forename: Ashish
authors.initials: A
authors.lastname: Mehta
authors.affiliation: National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.|DUKE-NUS Graduate Medical School.
authors.forename: Winston
authors.initials: W
authors.lastname: Shim
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*
keywords: cardiac progenitors; cardiac repair; cardiomyocytes; interstitial cells; telocytes