| Literature DB >> 33297443 |
Jacek Stępniewski1, Mateusz Tomczyk1, Kalina Andrysiak1, Izabela Kraszewska1, Alicja Martyniak1, Agnieszka Langrzyk1,2, Klaudia Kulik1,2, Ewa Wiśniewska1,2, Mateusz Jeż1, Urszula Florczyk-Soluch1, Katarzyna Polak1, Paulina Podkalicka1, Neli Kachamakova-Trojanowska3, Alicja Józkowicz1, Agnieszka Jaźwa-Kusior1, Józef Dulak1.
Abstract
Cell therapies are extensively tested to restore heart function after myocardial infarction (MI). Survival of any cell type after intracardiac administration, however, may be limited due to unfavorable conditions of damaged tissue. Therefore, the aim of this study was to evaluate the therapeutic effect of adipose-derived stromal cells (ADSCs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) overexpressing either the proangiogenic SDF-1α or anti-inflammatory heme oxygenase-1 (HO-1) in a murine model of MI. ADSCs and hiPSCs were transduced with lentiviral vectors encoding luciferase (Luc), GFP and either HO-1 or SDF-1α. hiPSCs were then differentiated to hiPSC-CMs using small molecules modulating the WNT pathway. Genetically modified ADSCs were firstly administered via intracardiac injection after MI induction in Nude mice. Next, ADSCs-Luc-GFP and genetically modified hiPSC-CMs were injected into the hearts of the more receptive NOD/SCID strain to compare the therapeutic effect of both cell types. Ultrasonography, performed on days 7, 14, 28 and 42, revealed a significant decrease of left ventricular ejection fraction (LVEF) in all MI-induced groups. No improvement of LVEF was observed in ADSC-treated Nude and NOD/SCID mice. In contrast, administration of hiPSC-CMs resulted in a substantial increase of LVEF, occurring between 28 and 42 days after MI, and decreased fibrosis, regardless of genetic modification. Importantly, bioluminescence analysis, as well as immunofluorescent staining, confirmed the presence of hiPSC-CMs in murine tissue. Interestingly, the luminescence signal was strongest in hearts treated with hiPSC-CMs overexpressing HO-1. Performed experiments demonstrate that hiPSC-CMs, unlike ADSCs, are effective in improving heart function after MI. Additionally, long-term evaluation of heart function seems to be crucial for proper assessment of the effect of cell administration.Entities:
Keywords: adipose-derived stromal cells; heme oxygenase-1; human induced pluripotent stem cells; myocardial infarction; stromal cell-derived factor-1α
Year: 2020 PMID： 33297443 PMCID： PMC7762393 DOI： 10.3390/biomedicines8120578
Source DB: PubMed Journal: Biomedicines ISSN： 2227-9059