کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2093689 1081973 2014 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Controlling Expansion and Cardiomyogenic Differentiation of Human Pluripotent Stem Cells in Scalable Suspension Culture
ترجمه فارسی عنوان
کنترل انقباض و اختلال قلب و عروق سلول های بنیادی پلورپوپتون در کشت سوبسترا مقیاس
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
چکیده انگلیسی


• Efficient cardiac differentiation protocol in suspension by chemical Wnt modulators
• Differentiation is CHIR concentration dependent, but aggregate size independent
• Bioreactor-controlled hPSC expansion dictates subsequent lineage differentiation
• Metallothionein is a potentially stress-induced marker of hPSC culture

SummaryTo harness the potential of human pluripotent stem cells (hPSCs), an abundant supply of their progenies is required. Here, hPSC expansion as matrix-independent aggregates in suspension culture was combined with cardiomyogenic differentiation using chemical Wnt pathway modulators. A multiwell screen was scaled up to stirred Erlenmeyer flasks and subsequently to tank bioreactors, applying controlled feeding strategies (batch and cyclic perfusion). Cardiomyogenesis was sensitive to the GSK3 inhibitor CHIR99021 concentration, whereas the aggregate size was no prevailing factor across culture platforms. However, in bioreactors, the pattern of aggregate formation in the expansion phase dominated subsequent differentiation. Global profiling revealed a culture-dependent expression of BMP agonists/antagonists, suggesting their decisive role in cell-fate determination. Furthermore, metallothionein was discovered as a potentially stress-related marker in hPSCs. In 100 ml bioreactors, the production of 40 million predominantly ventricular-like cardiomyocytes (up to 85% purity) was enabled that were directly applicable to bioartificial cardiac tissue formation.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 3, Issue 6, 9 December 2014, Pages 1132–1146
نویسندگان
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