کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8474739 | 1550431 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation
ترجمه فارسی عنوان
بهبود عملکرد و بلوغ بافت موش و انسانی قلب انسان با تحریک الکتریکی مزمن
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کلمات کلیدی
EHTMLC2vCardiomyocyte maturationhiPSCHpSCECMEC50engineered heart tissue - بافت قلب مهندسی شدهElectrical stimulation - تحریک الکتریکیfold change - تغییر در برابرHuman pluripotent stem cell - سلول بنیادی پلورپوفنت انسانیHuman induced pluripotent stem cell - سلول های بنیادی انعقادی انسانی بشرInduced pluripotent stem cells - سلول های بنیادی پرتوان القاییCardiomyocytes - قلب و عروقExtracellular matrix - ماتریکس خارج سلولیCardiac tissue engineering - مهندسی بافت قلبی2-Photon microscopy - میکروسکوپ 2-فوتونhalf maximal effective concentration - نیمه حداکثر غلظت موثرfractional shortening - کوتاه کردن کسری
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
چکیده انگلیسی
Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n = 96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n = 19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5 Hz developed 2.2 à higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca2 +-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2 Hz in the first week and 1.5 Hz thereafter developed 1.5 à higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 74, September 2014, Pages 151-161
Journal: Journal of Molecular and Cellular Cardiology - Volume 74, September 2014, Pages 151-161
نویسندگان
Marc N. Hirt, Jasper Boeddinghaus, Alice Mitchell, Sebastian Schaaf, Christian Börnchen, Christian Müller, Herbert Schulz, Norbert Hubner, Justus Stenzig, Andrea Stoehr, Christiane Neuber, Alexandra Eder, Pradeep K. Luther, Arne Hansen,