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Updated: May 24, 2026
Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
Long-term stable production of monocyte-colony inhibition factor (M-CIF) from CHO microcarrier perfusion cultures
1Human Genome Sciences, Inc., 9410 Key West Ave., Rockville, MD, 20850, U.S.A.
Abstract:
Monocyte-colony inhibition factor (M-CIF) was produced in microcarrier perfusion cultures from engineered Chinese hamster ovary (CHO) cells. Three and fifteen liter microcarrier perfusion bioreactors equipped with internal spin filters were operated for over two months. Approximately 60 L and 300 L of culture filtrate were harvested from the 3L and 15L microcarrier perfusion bioreactors respectively. During the perfusion operation, cell density reached 2-6 × 10(6) cells/ml. Importantly, stable expression of M-CIF from the CHO cells under non-selection condition was maintained at a level of 4-10 mg/L. Specific productivity was maintained at 1.8-3.4 mg/billion cells/day. The ability of the recombinant CHO cells to migrate from microcarrier to microcarrier under our proprietary HGS-CHO-3 medium greatly facilitated microcarrier culture scale-up and microcarrier replenishment. Future directions for microcarrier perfusion system scale-up and process development are highlighted.
Insights
Engineered Chinese hamster ovary (CHO) cells successfully produced monocyte-colony inhibition factor (M-CIF) in microcarrier perfusion cultures. This scalable bioprocess achieved high cell densities and stable M-CIF expression over extended culture durations.
Area of Science:
- Biotechnology
- Cell Culture Engineering
- Biopharmaceutical Production
Background:
- Monocyte-colony inhibition factor (M-CIF) is a key biopharmaceutical target.
- Optimizing production systems for recombinant proteins is crucial for biomanufacturing.
- Microcarrier perfusion culture offers potential for high-density cell cultivation.
Purpose of the Study:
- To evaluate the efficacy of microcarrier perfusion bioreactors for M-CIF production using engineered Chinese hamster ovary (CHO) cells.
- To assess the scalability and stability of M-CIF expression under perfusion conditions.
- To investigate cell behavior and culture dynamics in a long-term microcarrier perfusion system.
Main Methods:
- Utilized 3L and 15L microcarrier perfusion bioreactors with internal spin filters for over two months.
- Employed engineered Chinese hamster ovary (CHO) cells for the stable expression of M-CIF.
- Operated under proprietary HGS-CHO-3 medium to facilitate cell migration and microcarrier replenishment.
Main Results:
- Achieved high cell densities ranging from 2-6 × 10(6) cells/ml.
- Maintained stable M-CIF expression between 4-10 mg/L under non-selection conditions.
- Demonstrated specific productivity of 1.8-3.4 mg/billion cells/day.
- Harvested significant volumes of culture filtrate (60 L and 300 L from 3L and 15L bioreactors, respectively).
Conclusions:
- Microcarrier perfusion culture is a viable and scalable method for M-CIF production using engineered CHO cells.
- The system supports high cell densities and stable protein expression over extended periods.
- Cellular characteristics, such as microcarrier migration, are critical for successful scale-up and process robustness.
