Spinal Müsküler Atrofi durumunda iPSC Türevli Ventriküller Kardiyomiyositlerde Mitokondriyal Disfonksiyon


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Bitirim C. V., Olğar Y.

9th European Section Meeting of the International Academy of Cardiovascular Sciences (IACS-ES), Timisoara, Romanya, 4 - 07 Ekim 2023, ss.157

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Timisoara
  • Basıldığı Ülke: Romanya
  • Sayfa Sayıları: ss.157
  • Ankara Üniversitesi Adresli: Evet

Özet

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.