their adaptation to meet specific cell or process requirements. A

more comprehensive comparison between serum-containing and

chemically defined serum-free media can be found in Table 1.

Medium adaptability is important with regard to hMSC cultivation,

as studies have shown that, depending on the mesenchymal tissue

they were isolated from, the cells have very different requirements

regarding cell culture medium composition [45]. This observation

indicates that the development of various tissue-specific hMSC

media, as opposed to a universal approach, will be necessary in

future. Moreover, such aspects must be taken into consideration

to ensure not only that the target cell densities required for clinical

application are met but also that the desired cell quality is

maintained.

The implementation of chemically defined, serum-free media

also comes with its own challenges, however. Due to the absence of

serum as a shear stress protector, cells in dynamically mixed systems,

such as stirred bioreactors, are more sensitive to hydrodynamic

stress. This means that prior process characterization of the bio-

reactor systems, with respect to the cell culture medium and micro-

carrier selection, is essential and that choosing the appropriate

chemically defined serum-free medium or chemically defined basal

medium supplement should not be underestimated, especially

when working with hMSCs. Special attention should also be paid

to cell attachment efficiency, which may be lower without the

addition of serum. Personal experience has shown that chemically

defined cell culture medium composition has a strong influence on

Table 1

Comparison of serum containing medium and chemically defined, serum-free medium

Serum-containing medium

Chemically defined, serum-free medium

Advantages

Protection of cells from shear stress

Inoculation with lower cell densities possible

No lot-to-lot variability of composition

Far lower risk of contamination

Less laborious purification process

Easier validation and registration of

product

Disadvantages Chemically not defined and serum present

Lot-to-lot variability of composition

Potential sources of contamination (i.e.,

endotoxins, mycoplasma, prions)

More complicated purification process of

product

More difficult product validation and

registration process

Cells grown in serum free medium more

sensitive to hydrodynamic stresses

Choice and quantity of supplement (e.g.,

growth factors) strongly depend on the

cell type and process design

Examples

Any basal medium for mammalian cell

cultivation such as DMEM, α-MEM, or

RPMI 1640, supplemented to a total

serum content of 5–20%

UrSuppe (Cardiocentro Ticino)

Stemline^® XF (Merck)

StemPro™MSC SFM XenoFree (Gibco)

NutriStem MSC XF (biological

industries)

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Misha Teale et al.