|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|6450347||1415995||2017||14 صفحه PDF||سفارش دهید||دانلود رایگان|
- Human MSCs were expanded in a 50Â L bioreactor for 11Â days.
- A 43-fold expansion was attained with a yield of 1.28Â ÃÂ 1010 cells.
- The culture medium Î±MEM/PL is a xeno-free alternative to DMEM/FBS.
- Human MSCs from the bioreactor display similar properties to those grown in flasks.
The application of cell-based therapeutics requires development of refined and scalable culture processes. Stirred tank bioreactors facilitate growth of human mesenchymal stromal cells (hMSC) while meeting these needs. A process for expansion of hMSCs in a 50Â L bioreactor was developed. Parameters evaluated include agitation rate, pH and dissolved oxygen (DO) control set-points, and media formulation. The pH and DO levels were determined empirically in 3Â L bioreactors prior to implementation at the 50Â L scale. The agitation operating range for microcarrier cultures in the 50Â L bioreactor was calculated based on theoretical and empirical analyses of solid suspension and shear limitations. Additionally, small-scale experiments demonstrated that hMSC growth was improved in Î±MEM supplemented with human platelet lysate in comparison to DMEM supplemented with FBS. A 43-fold expansion of harvested hMSCs was achieved in 11Â days in a 50Â L bioreactor incorporating these process improvements. Cells expanded in the bioreactor exhibited the expected surface marker expression, trilineage differentiation potential, T cell growth inhibition and indoleamine 2,3-dioxygenase inducibility. The results highlight that identification of optimal pH, DO, agitation rates and culture medium for microcarrier-based bioreactor expansion of adherent cells is paramount to developing a platform to support cell-based therapies.
Journal: Biochemical Engineering Journal - Volume 120, 15 April 2017, Pages 49-62