Good manufacturing practice-compliant animal-free expansion of human bone marrow derived mesenchymal stroma cells in a closed hollow-fiber-based bioreactor |
| |
| Authors: | Philipp Nold Cornelia Brendel Andreas Neubauer Gregor Bein Holger Hackstein |
| |
| Affiliation: | 1. Dept. of Hematology, Oncology and Immunology, Philipps University Marburg and Universitätsklinikum Giessen und Marburg, Germany;2. Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University Giessen and Universitätsklinikum Giessen und Marburg, Germany;1. Department of Anaesthesiology, The University of Hong Kong, Hong Kong SAR, China;2. Attending anaesthesiologist, First Affiliated Hospital, Anhui Medical University, Auhui, China;1. CQM—Centro de Química da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9000-390 Funchal, Portugal;2. Centro Competências de Ciências Exactas e da Engenharia, Universidade da Madeira, Campus Universitário da Penteada, 9000-390 Funchal, Portugal;3. Research Unit and Cardiology Department, Dr. Nélio Mendonça Hospital, Avda. Luís de Camões, no. 57, 9050-514 Funchal, Portugal;1. Institute on Membrane Technology, National Research Council of Italy, 87036 Rende (CS), Italy;2. Department of Environmental and Chemical Engineering, University of Calabria, via P. Bucci Cubo 44/A, 87036 Rende (CS), Italy;1. Department of Hematology, Oncology and Immunology, Philipps University Marburg, Marburg, Germany;2. Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University Giessen, Giessen, Germany;3. Department for Biotechnology, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria;4. Institute of Molecular Biology and Tumor Research, Philipps University Marburg, Marburg, Germany;5. Department of Orthopedics and Rheumatology, Philipps University Marburg, Marburg, Germany |
| |
| Abstract: | Mesenchymal stroma cells (MSC) are increasingly recognized for various applications of cell-based therapies such as regenerative medicine or immunomodulatory treatment strategies. Standardized large-scale expansions of MSC under good manufacturing practice (GMP)-compliant conditions avoiding animal derived components are mandatory for further evaluation of these novel therapeutic approaches in clinical trials.We applied a novel automated hollow fiber cell expansion system (CES) for in vitro expansion of human bone marrow derived MSC employing a GMP-compliant culture medium with human platelet lysate (HPL). Between 8 and 32 ml primary bone marrow aspirate were loaded into the hollow fiber CES and cultured for 15–27 days. 2–58 million MSC were harvested after primary culture. Further GMP-compliant cultivation of second passage MSC for 13 days led to further 10–20-fold enrichment. Viability, surface antigen expression, differentiation capacity and immunosuppressive function of MSC cultured in the hollow fiber CES were in line with standard criteria for MSC definition. We conclude that MSC can be enriched from primary bone marrow aspirate in a GMP-conform manner within a closed hollow fiber bioreactor and maintain their T lymphocyte inhibitory capacity. Standardized and reliable conditions for large scale MSC expansion pave the way for safe applications in humans in different therapeutic approaches. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
