title: iPSC-derived human mesenchymal stem cells improve myocardial strain of infarcted myocardium.
abstract: We investigated global and regional effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) in infarcted myocardium. Acute myocardial infarction (MI) was induced by ligation of left coronary artery of severe combined immunodeficient mice before 2 × 10(5) iMSCs or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Global and regional myocardial function was assessed serially at 1-week and 8-week by segmental strain analysis by using two dimensional (2D) speckle tracking echocardiography. Early myocardial remodelling was observed at 1-week and persisted to 8-week with global contractility of ejection fraction and fractional area change in saline- (32.96 ± 14.23%; 21.50 ± 10.07%) and iMSC-injected (32.95 ± 10.31%; 21.00 ± 7.11%) groups significantly depressed as compared to sham control (51.17 ± 11.69%, P < 0.05; 34.86 ± 9.82%, P < 0.05). However, myocardial dilatation was observed in saline-injected animals (4.40 ± 0.62 mm, P < 0.05), but not iMSCs (4.29 ± 0.57 mm), when compared to sham control (3.74 ± 0.32 mm). Furthermore, strain analysis showed significant improved basal anterior wall strain (28.86 ± 8.16%, P < 0.05) in the iMSC group, but not saline-injected (15.81 ± 13.92%), when compared to sham control (22.18 ± 4.13%). This was corroborated by multi-segments deterioration of radial strain only in saline-injected (21.50 ± 5.31%, P < 0.05), but not iMSC (25.67 ± 12.53%), when compared to sham control (34.88 ± 5.77%). Improvements of the myocardial strain coincided with the presence of interconnecting telocytes in interstitial space of the infarcted anterior segment of the heart. Our results show that localized injection of iMSCs alleviates ventricular remodelling, sustains global and regional myocardial strain by paracrine-driven effect on neoangiogenesis and myocardial deformation/compliance via parenchymal and interstitial cell interactions in the infarcted myocardium.
authors: National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
authors: Qingfeng
authors: Q
authors: Miao
authors: Winston
authors: W
authors: Shim
authors: Nicole
authors: N
authors: Tee
authors: Sze Yun
authors: SY
authors: Lim
authors: Ying Ying
authors: YY
authors: Chung
authors: K P Myu Mia
authors: KP
authors: Ja
authors: Ting Huay
authors: TH
authors: Ooi
authors: Grace
authors: G
authors: Tan
authors: Geraldine
authors: G
authors: Kong
authors: Heming
authors: H
authors: Wei
authors: Chong Hee
authors: CH
authors: Lim
authors: Yoong Kong
authors: YK
authors: Sin
authors: Philip
authors: P
authors: Wong
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology*; D020257:Ventricular Remodeling / Q000502:physiology*
keywords: cell therapy; myocardial compliance; myocardial strain; telocytes; tissue deformation