Intracellular transduction of TAT-Hsp27 fusion protein enhancing cell survival and regeneration capacity of cardiac stem cells in acute myocardial infarction
| Autor: | Kwang Suk Lim, Eun-Jung Kim, Jong Tae Kim, Yong-Hee Kim, Wonjin Lee, Ki Dong Park, Hye Jung Kim, Myoung Hun Kim, Jang Kyoung Kim, Young Il Yang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
endocrine system animal structures Cell Survival HSP27 Heat-Shock Proteins Myocardial Infarction Pharmaceutical Science Apoptosis Antioxidants Rats Sprague-Dawley Heart disorder Transduction (genetics) Hsp27 In vivo Transduction Genetic Animals Regeneration Heat-Shock Proteins biology Dose-Response Relationship Drug Hematopoietic Stem Cells Rats Caspases Immunology Acute Disease Gene Products tat Cancer research biology.protein Signal transduction Stem cell Reactive Oxygen Species Viral Fusion Proteins Ex vivo Intracellular Molecular Chaperones |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 215 |
| ISSN: | 1873-4995 |
| Popis: | Myocardial infarction (MI) results in the substantial loss of functional cardiomyocytes, which frequently leads to intractable heart disorders. Cardiac stem cells (CSCs) that retain the capacity to replace all cardiac cells might be a promising strategy for providing a source of new functional cardiomyocytes; however, the poor survival and engraftment of transplanted CSCs in the hostile environment of MI critically mitigate their therapeutic benefits. To capitalize their therapeutic potential, an ex vivo strategy in which CSCs were introduced to the recombinant heat shock protein 27 (Hsp27) through a TAT protein transduction domain for increasing the viability and engraftment in the infarcted myocardium was designed. A recombinant TAT fused Hsp27 (TAT-Hsp27) was able to enter CSCs in a dose-dependent manner. CSCs transduced with TAT-Hsp27 expressed not only endogenous Hsp27 but externally introduced Hsp27, resulting in substantial increase of their anti-oxidative and anti-apoptotic properties via suppressing reactive oxygen species production, the MAPKs signaling pathway, and caspase activation. TAT-Hsp27 enabled CSCs to be protected from apoptotic- and hypoxic-induced cell death during in vitro cardiomyogenic differentiation. In vivo studies demonstrated that CSCs transduced TAT-Hsp27 significantly increased the survival and engraftment in the acutely infarcted myocardium, which is closely related to caspase activity suppression. Finally, CSCs transduced TAT-Hsp27 improved cardiac function and attenuated cardiac remodeling in comparison with non-transduced CSCs. Overall, our approach, which is based on the ex vivo intracellular transduction of TAT-Hsp27 into CSCs before myocardial delivery, might be effective in treating MI. |
| Databáze: | OpenAIRE |
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