論文 - 詳細
| RRC ID | 38251 |
|---|---|
| 著者 | Kawaguchi N, Smith AJ, Waring CD, Hasan MK, Miyamoto S, Matsuoka R, Ellison GM. |
| タイトル | c-kitpos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival through IGF-1 paracrine signalling. |
| ジャーナル | PLoS One |
| Abstract |
BACKGROUND:Resident c-kit positive (c-kitpos) cardiac stem cells (CSCs) could be considered the most appropriate cell type for myocardial regeneration therapies. However, much is still unknown regarding their biological properties and potential. METHODOLOGY/PRINCIPAL FINDINGS:We produced clones of high and low expressing GATA-4 CSCs from long-term bulk-cultured c-kitpos CSCs isolated from adult rat hearts. When c-kitpos GATA-4 high expressing clonal CSCs (cCSCs) were co-cultured with adult rat ventricular cardiomyocytes, we observed increased survival and contractility of the cardiomyocytes, compared to cardiomyocytes cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low expressing cCSCs. When analysed by ELISA, the concentration of IGF-1 was significantly increased in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-cultures and there was a significant correlation between IGF-1 concentration and cardiomyocyte survival. We showed the activation of the IGF-1 receptor and its downstream molecular targets in cardiomyocytes co-cultured with c-kitpos GATA-4 high cCSCs but not in cardiomyocytes that were cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low cCSCs. Addition of a blocking antibody specific to the IGF-1 receptor inhibited the survival of cardiomyocytes and prevented the activation of its signalling in cardiomyocytes in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-culture system. IGF-1 supplementation or IGF-1 high conditioned medium taken from the co-culture of c-kitpos GATA-4 high cCSCs plus cardiomyocytes did extend the survival and contractility of cardiomyocytes cultured alone and cardiomyocytes co-cultured with c-kitpos GATA-4 low cCSCs. CONCLUSION/SIGNIFICANCE:c-kitpos GATA-4 high cCSCs exert a paracrine survival effect on cardiomyocytes through induction of the IGF-1R and signalling pathway. |
| 巻・号 | 5(12) |
| ページ | e14297 |
| 公開日 | 2010-12-13 |
| DOI | 10.1371/journal.pone.0014297 |
| PMID | 21179204 |
| PMC | PMC3001457 |
| MeSH | Animals Cell Culture Techniques / methods Cell Survival Cell- and Tissue-Based Therapy / methods* GATA4 Transcription Factor / metabolism* Heart / physiology Insulin-Like Growth Factor I / metabolism* Myocardium / cytology* Myocytes, Cardiac / cytology* Paracrine Communication Proto-Oncogene Proteins c-kit / metabolism* Rats Regeneration / physiology* Signal Transduction Stem Cells / metabolism* |
| IF | 2.74 |
| 引用数 | 58 |
| WOS 分野 | CARDIAC & CARDIOVASCULAR SYSTEMS |
| リソース情報 | |
| ヒト・動物細胞 | Rat-1(RCB1830) |