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The generation of cardiosphere from adult heart and the implication of LPAR4+ cardiac progenitor cells for the treatment in ischemic heart disease
허혈성 심장질환 치료를 위한 심장유래 cardiosphere와 LPA수용체4 + 심근전구세포의 영향에 관한 연구

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Authors
이호재
Advisor
김효수
Major
의과대학 의과학과
Issue Date
2015-02
Publisher
서울대학교 대학원
Keywords
cardiac progenitor cellscardiospheres
Description
학위논문 (박사)-- 서울대학교 대학원 : 의과학과, 2015. 2. 김효수.
Abstract
Cardiac stem cells are found only in small numbers in the adult heart. As a strategy to overcome the limitation of insufficient cell numbers, cardiosphere-derived cells (CDCs) have been previously introduced. Since two-dimensional CDCs showed lower stemness than 3-dimensional form, re-creating sphere from attached CDCs could overcome such barrier. Nevertheless, repeated primary culture remains as technical huddle due to passage-dependent loss of stemness. Here, I proposed a method for stemness recovery by 3-dimensional culture, and an extension strategy for enriched number of phase-bright cells obtained from heart tissue by ex vivo culture.
To screen a specific marker of phase-bright cells, microarray data analysis was performed. Lysophosphatidic acid receptor 4 (LPAR4) was increased in most of phase-bright cells. A higher number of phase-bright cells were generated after treatment of 1μM LPA. Simultaneously, the expression of stemness related genes were increased together in a 3-dimensional form and by LPA treatment. The LPAR4 expressed phase-bright cells cultured in 3-dimension were then differentiated into cardiomyocytes. FACS analysis showed that the markers of cardiomyocyte, troponin-T andα-SA were more highly expressed than differentiation of CDC control group.
In conclusion, the acquired phase-bright cells with sufficient cell number and 3-dimensional form can be useful for differentiation into cardiomyocyte. The expression of LPAR4 in adult cardiac progenitors associates with the activation of cardiac progenitor cells for the differentiation into cardiomyocyte.
Language
English
URI
https://hdl.handle.net/10371/122272
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Theses (Ph.D. / Sc.D._의과학과)
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