Finding the design space of a filtration-based operation for the concentration of human pluripotent stem cells

作者: Bárbara Cunha , Ricardo JS Silva , Cláudia Correia , Alexey Koshkin , Paula M Alves

DOI: 10.1016/J.MEMSCI.2017.08.036

关键词:

摘要: Abstract Process knowledge for designing robust and reproducible unit operations is essential, especially complex biological systems. This work describes a shortcut approach the design of tangential flow filtration concentration human induced pluripotent stem cells (hiPSC), supported by experiments. Critical process parameters (CPP) shear rate, permeate flux cell load were considered, their impact on hiPSC recovery yield viability was studied. A full factorial confirmed significant interaction effects between all CPP, affecting both responses. The developed statistical model predicted that high rate (3000 s −1 ), (250 LMH) medium (2 × 10 6  cell/cm 2 ) would maximize viability, where over 80% recovered after volume reduction factor 20 with (over 93%). Such conditions validated experimentally, performing robustness analysis, success these operating assessed (65–70%). parametric study then conducted, identifying increasing (up to 3370 s allowed achieve specified requirements (>80%) (>90%) in 100% cases no hiPSC's identity, proliferation capacity pluripotency observed.

参考文章(22)
Alan Trounson, Courtney McDonald, Stem Cell Therapies in Clinical Trials: Progress and Challenges Cell Stem Cell. ,vol. 17, pp. 11- 22 ,(2015) , 10.1016/J.STEM.2015.06.007
Sally Hassan, Ana S Simaria, Hemanthram Varadaraju, Siddharth Gupta, Kim Warren, Suzanne S Farid, Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions Regenerative Medicine. ,vol. 10, pp. 591- 609 ,(2015) , 10.2217/RME.15.29
Barbara Cunha, Tiago Aguiar, Marta M Silva, Ricardo JS Silva, Marcos FQ Sousa, Earl Pineda, Cristina Peixoto, Manuel JT Carrondo, Margarida Serra, Paula M Alves, None, Exploring continuous and integrated strategies for the up- and downstream processing of human mesenchymal stem cells Journal of Biotechnology. ,vol. 213, pp. 97- 108 ,(2015) , 10.1016/J.JBIOTEC.2015.02.023
Shannon Eaker, Myriam Armant, Harvey Brandwein, Scott Burger, Andrew Campbell, Carmine Carpenito, Dominic Clarke, Timothy Fong, Ohad Karnieli, Knut Niss, Wouter Van't Hof, Ravenska Wagey, Concise Review: Guidance in Developing Commercializable Autologous/Patient-Specific Cell Therapy Manufacturing Stem Cells Translational Medicine. ,vol. 2, pp. 871- 883 ,(2013) , 10.5966/SCTM.2013-0050
Ana M. Martins, Gordana Vunjak-Novakovic, Rui L. Reis, The Current Status of iPS Cells in Cardiac Research and Their Potential for Tissue Engineering and Regenerative Medicine Stem Cell Reviews and Reports. ,vol. 10, pp. 177- 190 ,(2014) , 10.1007/S12015-013-9487-7
Gaia Franceschini, Sandro Macchietto, Model-based design of experiments for parameter precision: State of the art Chemical Engineering Science. ,vol. 63, pp. 4846- 4872 ,(2008) , 10.1016/J.CES.2007.11.034
Bárbara Cunha, Cristina Peixoto, Marta M. Silva, Manuel J.T. Carrondo, Margarida Serra, Paula M. Alves, Filtration methodologies for the clarification and concentration of human mesenchymal stem cells Journal of Membrane Science. ,vol. 478, pp. 117- 129 ,(2015) , 10.1016/J.MEMSCI.2014.12.041
Akon Higuchi, Qing-Dong Ling, S. Suresh Kumar, Murugan Munusamy, Abdullah A. Alarfajj, Akihiro Umezawa, Gwo-Jang Wu, Design of polymeric materials for culturing human pluripotent stem cells: Progress toward feeder-free and xeno-free culturing Progress in Polymer Science. ,vol. 39, pp. 1348- 1374 ,(2014) , 10.1016/J.PROGPOLYMSCI.2014.01.002
Anurag S Rathore, Helen Winkle, Quality by design for biopharmaceuticals Nature Biotechnology. ,vol. 27, pp. 26- 34 ,(2009) , 10.1038/NBT0109-26