Scale-up manufacturing of gelatin-based microcarriers for cell therapy
| Autor: | Pere Dosta, Yi Zhang, Kui Wang, Nicholas Uth, Eytan Abraham, Shiran Ferber, Albert Ros, Natalie Artzi, Yonatan Levinson |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
food.ingredient Materials science Biomedical Engineering Cell Culture Techniques Cell- and Tissue-Based Therapy Gelatin Biomaterials Cell therapy 03 medical and health sciences Laboratory flask 0302 clinical medicine food Bioreactors Bioreactor Humans Dissolution Cell growth Mesenchymal stem cell technology industry and agriculture Microcarrier Mesenchymal Stem Cells Cells Immobilized Microspheres 030104 developmental biology Chemical engineering 030220 oncology & carcinogenesis |
| Zdroj: | Journal of biomedical materials research. Part B, Applied biomaterialsREFERENCES. 108(7) |
| ISSN: | 1552-4981 |
| Popis: | Microcarriers, including crosslinked porous gelatin beads (Cultispher G) are widely used as cell carriers for cell therapy applications. Microcarriers can support a range of adherent cell types in stirred tank bioreactor culture, which is scalable up to several thousands of liters. Cultispher G in particular is advantageous for cell therapy applications because it can be dissolved enzymatically, and thus cells can be harvested without the need to perform a large-scale cell-bead filtration step. This enzymatic dissolution, however, is challenged by the slow degradation of the carriers in the presence of enzymes as new extracellular matrix is being deposited by the proliferating cells. This extended dissolution timelimits the yield of cell recovery while compromising cellular viability. We report herein the development of crosslinked porous gelatin beads that afford rapid, stimuli-triggered dissolution for facile cell removal using human mesenchymal stem cells (hMSC) as a model system. We successfully fabricated redox-sensitive beads (RS beads) and studied their cell growth, dissolution time and cell yield, compared to regular gelatin-based beads (Reg beads). We have shown that RS beads allow for much faster dissolution compared to Reg beads, supporting better hMSC detachment and recovery following 8 days of culture in spinner flasks, or in 3L bioreactors. These newly synthesized RS beads show promise as cellular microcarriers and can be used for scale-up manufacturing of different cell types while providing on-demand degradation for facile cell retrieval. |
| Databáze: | OpenAIRE |
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