Arterial Delivery of Genetically Labelled Skeletal Myoblasts to the Murine Heart: Long-Term Survival and Phenotypic Modification of Implanted Myoblasts
| Autor: | S W, Robinson, P W, Cho, H I, Levitsky, J L, Olson, R H, Hruban, M A, Acker, P D, Kessler |
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| Rok vydání: | 1996 |
| Předmět: |
Male
0301 basic medicine Time Factors Transplantation Heterotopic Muscle Fibers Skeletal Biomedical Engineering lcsh:Medicine Transfection Cell Line Mice 03 medical and health sciences Escherichia coli Animals Muscle Skeletal Mice Inbred C3H Transplantation 030102 biochemistry & molecular biology Calcium-Binding Proteins Graft Survival lcsh:R Heart Cell Biology beta-Galactosidase musculoskeletal system Recombinant Proteins Microscopy Electron 030104 developmental biology Connexin 43 Biomarkers |
| Zdroj: | Cell Transplantation, Vol 5 (1996) |
| ISSN: | 1555-3892 0963-6897 |
| DOI: | 10.1177/096368979600500113 |
| Popis: | The ability to replace damaged myocardial tissue with new striated muscle would constitute a major advance in the treatment of diseases that irreversibly injure cardiac muscle cells. The creation of focal grafts of skeletal muscle has been reported following the intramural injection of skeletal myoblasts into both normal and injured myocardium. The goals of this study were to determine whether skeletal myoblast-derived cells can be engrafted into the murine heart following arterial delivery. The murine heart was seeded with genetically labeled C2C12 myoblasts introduced into the arterial circulation of the heart via a transventricular injection. A transventricular injection provided access to the coronary and systemic circulations. Implanted cells were characterized using histochemical staining for β-galactosidase, immunofluorescent staining for muscle-specific antigens, and electron microscopy. Initially the injected cells were observed entrapped in myocardial capillaries. One week after injection myoblasts were present in the myocardial interstitium and were largely absent from the myocardial capillary bed. Implanted cells underwent myogenic development, characterized by the expression of a fast-twitch skeletal muscle sarco-endoplasmic reticulum calcium ATPase (SERCA1) and formation of myofilaments. Four months following injection myoblast-derived cells began to express a slow-twitch/cardiac protein, phospholamban, that is normally not expressed by C2C12 cells in vitro. Most surprisingly, regions of close apposition between LacZ labeled cells and native cardiomyocytes contained structures that resembled desmosomes, fascia adherens junctions, and gap junctions. The cardiac gap junction protein, connexin43, was localized to some of the interfaces between implanted cells and cardiomyocytes. Collectively, these findings suggest that arterially delivered myoblasts can be engrafted into the heart, and that prolonged residence in the myocardium may alter the phenotype of these skeletal muscle-derived cells. Further studies are necessary to determine whether arterial delivery of skeletal myoblasts can be developed as treatment for myocardial dysfunction. |
| Databáze: | OpenAIRE |
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