9th European Section Meeting of the International Academy of Cardiovascular Sciences (IACS-ES), Timisoara, Romanya, 4 - 07 Ekim 2023, ss.157
Background & Aim: Clinical and preclinical studies reported insufficient cell engraftment
and delayed cardiac functional recovery problems in stem cell-based therapy in heart failure.
Therefore, pretreatment of stem cells with an exogenous factor may improve regenerative
efficiency. Here we aimed to induce the transplantation efficiency and regenerative capacity of
cardiac progenitor cells (CPCs) through estrogen administration.
Materials & Methods: CPCs were isolated from a male mouse heart and incubated with
estrogen (E2:10-7M, 48hours) in vitro. The heart failure model was generated by
intraperitoneally isoproterenol treatment (ISO;200mg/kg, 6days) in the female mouse. Either
estrogen pretreated-CPC (E2-CPC) or untreated-CPCs were intramyocardially transplanted
into the failure heart. Engraftment and retention levels of transplanted cells were visualized by
IVIS and SRY gene for expression analysis. Electrophysiological changes were analyzed by
echocardiographic analysis (ECG) before and after the ISO application. Cardiac regeneration
status following the transplantation was also examined at the molecular level through both
qRT-PCR from isolated heart samples and immunofluorescence/histochemical staining on
heart tissue sections to address the efficiency of the estrogen pre-treated CPC transplantation.
Results: Our IVIS and PCR results have demonstrated that untreated-CPCs diffuse much more
rapidly in the heart compared to E2-CPCs. At the end of the 24hours after transplantation, only
E2-CPCs were detected in the heart. ECG recordings showed that PR, QT, and QRS-intervals
were markedly prolonged in ISO-treated mice. These intervals significantly shortened in E2-
CPC transplanted mouse hearts compared to the untreated-CPC transplanted group. E2-CPC
transplantation also remarkably reduced the collagen and lipid accumulation in the heart
tissues. Our observations also showed that E2-CPC transfer induced cardiomyocyte
proliferation and neo-vasculogenesis in transplanted hearts compared to the untreated-CPC
group via increasing the Ki67, CXCR, cTNTI, and vWF protein expression levels.
Conclusion: Here, we demonstrated the effect of estrogen administration on the regenerative
capacity of CPCs with in vitro and in vivo experiments.