노화된 간의 수복을 위한 miRNA 기반 치료용 재건줄기세포 생체내 유도기술 개발에 관한 연구 = Development of In vivo induction technology for miRNA-based regenerative stem cell therapy for liver repair in aging

다국어 초록 (Multilingual Abstract)

Background: Cellular senescence in hepatocytes impairs liver regeneration and promotes fibrosis. Mesenchymal stem cells (MSCs) demonstrate potential for liver regeneration, and microRNAs (miRNAs) may augment this therapeutic effect. This study investigates miRNA- based therapies for hepatic fibrosis and regeneration.
Methods: Mitochondrial function was assessed by Seahorse assay, while miRNA expression, senescence, and protein expression were evaluated by RT-qPCR, SA-β-gal staining, and immunohistochemistry/Western blot, respectively. Liver injury was induced in mice, and serum AST/ALT levels were analyzed.
Results: This study explored the aging processes occurring during stem cell culture and potential mitigation strategies. Serial passaging of stem cells resulted in morphological alterations, diminished differentiation capacity, mitochondrial dysfunction, and elevated beta- galactosidase activity. Analysis of miR-210 revealed its critical role in stem cell mitochondrial function and senescence. Inhibition of miR-210 rejuvenated aged stem cell function, improved mitochondrial dynamics, and enhanced hepatic function. This study underscores the potential of miRNA-based stem cell regeneration therapies, establishing a crucial foundation for future therapeutic development.
Conclusions: This study proposes utilizing miR-210 to mitigate stem cell aging and the associated functional decline. Stem cell passage promotes aging, marked by mitochondrial dysfunction and diminished pluripotency marker expression, further exacerbated by increased miR-210 expression. Inhibition of miR-210 restores mitochondrial function and enhances liver regeneration. This research indicates that miR-210 inhibition can restore stem cell regenerative potential and may offer a therapeutic approach for liver disease.

목차 (Table of Contents)

• Abstract i
• List of Table and figures iii
• Introduction 1
• Materials and methods 4
• Results 8
• Discussion 12
• Figure legends 18
• References 23
• 국문요약 25
• List of Table and figures
• Table 1 23
• Figure 1 24
• Figure 2 25
• Figure 3 26
• Figure 4 27
• Figure 5 28