Abstract
BackgroundCell-based therapies have the potential to become treatment options for many diseases, but efficient scale-out of these therapies has proven to be a major hurdle. Bioreactors can be used to overcome this hurdle, but changing the culture method can introduce unwanted changes to the cell product. Therefore, it is important to establish parity between products generated using traditional methods versus those generated using a bioreactor.MethodsMesenchymal stromal cells (MSCs) are cultured in parallel using either traditional culture flasks, spinner vessels or a new bioreactor system. To investigate parity between the cells obtained from different methods, harvested cells are compared in terms of yield, phenotype and functionality.ResultsBioreactor-based expansion yielded high cell numbers (222–510 million cells). Highest cell expansion was observed upon culture in flasks [average 5.0 population doublings (PDL)], followed by bioreactor (4.0 PDL) and spinner flasks (3.3 PDL). Flow cytometry confirmed MSC identity (CD73+, CD90+ and CD105+) and lack of contaminating hematopoietic cell populations. Cultured MSCs did not display genetic aberrations and no difference in differentiation and immunomodulatory capacity was observed between culture conditions. The response to IFNγ stimulation was similar for cells obtained from all culture conditions, as was the capacity to inhibit T cell proliferation.ConclusionsThe new bioreactor technology can be used to culture large amounts of cells with characteristics equivalent to those cultured using traditional, flask based, methods.
Highlights
Cell-based therapies have the potential to become treatment options for many diseases, but efficient scale-out of these therapies has proven to be a major hurdle
For one cell therapy medicinal product (CTMP) manufacturing process to be replaced by another, parity between the cell products from both processes needs to be established [7]. We demonstrate that these bioreactor-expanded Mesenchymal stromal cells (MSCs) populations are phenotypically similar to flask- and spinner-expanded
Initiation of bone marrow culture MSC cultures were initiated from bone marrow aspirates derived from five different donors
Summary
Cell-based therapies have the potential to become treatment options for many diseases, but efficient scale-out of these therapies has proven to be a major hurdle. Bioreactors can be used to overcome this hurdle, but changing the culture method can introduce unwanted changes to the cell product. Cell-based therapies have the potential to become treatment options for many diseases [1], but efficient scaleout of these therapies has proven to be a major hurdle [2, 3]. Several alternatives that aim to address the specific problems associated with flask culture have come to market. These include stacked and multi-layered flask systems, as well as various bioreactor systems. It is crucial to investigate whether proposed new culture methods result in a product that is comparable in terms of identity, safety and potency [7]
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