Biomedical Engineering Reference
In-Depth Information
If cell growth is unexpectedly slow during expansion culture, clinicians have to
waste precious time waiting for its recovery, and cannot schedule the operation.
During this process, costly consumables are wasted, and future cell behavior is
most likely unpredictable. If cellular activity (e.g., differentiation rate, cellular
growth, protein production, etc.) is disturbed by unresolved technical errors, the
therapeutic effects of the cells will not be as expected. Hence, the many unsolved
problems associated with quality assurance in clinical cell therapy should be
conquered by technological achievements.
Despite the existence of such ambiguous problems in clinical cell therapy,
conventional assay technologies in biology have not yet conquered any of these
problems. Furthermore, conventional molecular biology assay techniques are
basically incompatible with the production of cellular products, because they lack
the 4 major characteristics listed below.
The first and the most fundamental criterion is non-invasiveness. Cells for
clinical application should be as intact as possible, because the artificial manip-
ulation process itself could trigger cellular abnormalities. In addition, cells derived
from patients are usually limited, considering the limited source of cells and
reduction in the patient's load during collection of source cells. For greater safety,
fluorescent staining or gene transfer should be avoided.
The second characteristic is exhaustiveness. In clinical cell therapy, ''sampling
check'' is a commonly used method for cell assessment. However, compared to
chemical compound production, human cells exhibit huge variances; hence, partial
sampling will not assure the quality of the cell population. Therefore, assessment
of cells used for clinical purposes should shift to ''total cell assessment'' with
technological advances.
The third property is synchronism. Given that cultured cells differ drastically
with respect to their individual mobility, duplication, senescence, differentiation,
and production activity, end-point assays are associated with high error rates.
Kinetic examination is expected to detect small irregularities in cells for moni-
toring cellular status and optimizing cell culture conditions. High error rates
together with the lack of speed limits the use of end-point assays. Most cellular
contamination checks require hours, days, or weeks. This problem forces
the patients to wait to be informed of problems in the implanted cells until after the
operation. For practical cellular assessment, ''on-time'' evaluation right before the
operation would strongly assist the doctors.
The fourth characteristic is correlation with future status. However accurate the
on-time monitoring results of conventional assays may be, they do not quantita-
tively predict the future state. Therefore, in the cell production process, planning
effective protocols to revise the current cell culture process for better production is
extremely difficult. To enable the smooth operation of clinical cell therapy, future
state prediction would facilitate the development of new clinical protocols.
Because cells are not uniform and change with time, the culturing process should
be optimized in an ongoing manner using effective ''feedback information'' with
the future results in mind. Such a feedback information loop of cell quality
information will improve the quality of the final cellular product, resulting in
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