کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10228095 473 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phenotypic modulation of human cardiospheres between stemness and paracrine activity, and implications for combined transplantation in cardiovascular regeneration
ترجمه فارسی عنوان
مدولاسیون فنوتیپی قارچ شناختی انسان در بین ساقه و فعالیت پاراکرین و پیامدهای پیوند ترکیبی در بازسازی قلب و عروق
کلمات کلیدی
سلول بنیادی قلب، سلول پیش ساز قلب، قلب و عروق، پیوند سلولی، انفارکتوس میوکارد،
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
چکیده انگلیسی
As the search for new cell types for cardiovascular regeneration continues, it has become increasingly important to optimize ex vivo cell processing. We aimed to develop an optimal processing strategy for human cardiac progenitor cells. We hypothesized that enhancing the stemness potential and promoting the secretory activity for paracrine effects are mutually exclusive routes. Therefore, we investigated the two divergent cell processing methods to enhance cellular potency and humoral activity, respectively. We obtained human right ventricular tissues and sequentially generated primary cardiosphere (CS), primary CS-derived cells (PCDC) and secondary CSs. During secondary CS formation, inhibiting the ERK pathway, using selective RTK1 and TGF-β inhibitors, Oct4 increased 20 fold and VEGF was decreased. When the ERK pathway was stimulated by addition of EGF and TGF-β, VEGF expression was upregulated and Oct4 was downregulated, indicating that the ERK pathway serves a directional role for cellular potency versus paracrine capacity. Transplantation of PCDCs or secondary CSs into the infarcted heart of immunocompromised mouse showed significant angiogenic effects compared with PBS injection. Interestingly, combined transplantation of the two differently-processed, dual-purpose secondary CSs resulted in an additional increase in neovascularization. Human VEGF was primarily produced from secondary CSs under ERK stimulating conditions. Cardiomyocyte-like cells were produced from secondary CSs under ERK inhibitory conditions. These findings indicate that combined transplantation of specifically-processed human secondary CSs enhances infarct repair through the complementary enhancement of cardiopoietic regenerative and paracrine protective effect. Furthermore, these results underscore the fact that optimal cell processing methods have the potential to maximize the therapeutic benefits.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 34, Issue 38, December 2013, Pages 9819-9829
نویسندگان
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