کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6156027 | 1597939 | 2016 | 47 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
In vitro expansion of human cardiac progenitor cells: exploring 'omics tools for characterization of cell-based allogeneic products
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کلمات کلیدی
CSCHGFR-PhycoerythrinIL-8SOD2TPM2IGF-IμmaxXmaxATMPHCPCFITCFDACCL22DE - 2de2-D electrophoresis - الکتروفورز 2-DInterleukin 8 - اینترلوکین 8matrix-assisted laser desorption/ionization - جذب / یونیزاسیون لیزر ماتریس کمک می کندMaximum growth rate - حداکثر سرعت رشدfluorescein diacetate - دی فسفات فلورسینCardiac stem cells - سلول های بنیادی قلبMass spectrometry - طیف سنجی جرمیHepatocyte growth factor - عامل رشد هپاتوسیتinsulin-like growth factor 1 - فاکتور رشد مانند انسولین 1Fluorescein - فلورسئینCardiomyocytes - قلب و عروقProgrammed death ligand 1 - لیگاند مرگ برنامه ریزی شده 1MALDI - مالدیPropidium iodide - پروتئین یدیدchemokine (C-C motif) ligand 2 - کیموکین (C-C motif) لیگاند 2
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Human cardiac stem/progenitor cells (hCPCs) have been shown to be capable to regenerate contractile myocardium. However, because of their relative low abundance in the heart, in vitro expansion of hCPC is mandatory to achieve necessary quantities for allogeneic or autologous cardiac regeneration therapy applications (106-109 cells/patient). Up to now, cell number requirements of ongoing phase I/IIa trials have been fulfilled with production in static monolayer cultures. However, this manufacturing process poses critical limitations when moving to the following clinical phases where hundreds of patients will be enrolled. For this, increased process yield is required, while guaranteeing the quality of the cell-based products. In this work, we developed and validated a robust, scalable, and good manufacturing practice (GMP)-compatible bioprocess for the expansion of high-quality hCPC. We applied platforms extensively used by the biopharmaceutical industry, such as microcarrier technology and stirred systems, and assessed culture conditions' impact on hCPC's quality and potency, as required by regulatory agencies. Complementary analytical assays including gene expression microarrays and mass spectrometry-based approaches were explored to compare transcriptome, proteome, surface markers, and secretion profiles of hCPC cultured in static monolayers and in stirred microcarrier-based systems. Our results show that stirred microcarrier-based culture systems enabled achieving more than 3-fold increase in hCPC expansion, when compared with traditional static monolayers, while retaining cell's phenotype and similar “omics” profiles. These findings demonstrate that this change in the production process does not affect cell's identity and quality, with potential to be translated into a transversal production platform for clinical development of stem-cell therapies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Translational Research - Volume 171, May 2016, Pages 96-110.e3
Journal: Translational Research - Volume 171, May 2016, Pages 96-110.e3
نویسندگان
P. Gomes-Alves, M. Serra, C. Brito, C.P. Ricardo, R. Cunha, M.F. Sousa, B. Sanchez, A. Bernad, M.J.T. Carrondo, L. Rodriguez-Borlado, P.M. Alves,