Biomedical Engineering Reference
In-Depth Information
including a potential stand-by phase in liquid nitrogen. This process results in chondrocyte-
based medicinal products (a combination of cells and collagen-based membranes) with
defined identity and stability that make them suitable for ACI therapeutical option in
patients with articular cartilage damages. The Authors haver three main comments to
disclose, based on this experience. The first is about the use of FBS in culture which, besides
animal origin related problems, may imply immune responses in patients. We justify our
choice to use FBS in monolayer conditions because it allowed a better cell growth
standardization. However, since its potentially dangerous action could not be ignored, we
decided to avoid FBS presence in the final products. This resolution was supported by
validation data that were showing that the engineered tissues were cartilage-like also
without this supplement. These results revealed to be in line with the literature and with
data obtained by the Authors themselves with other chondrocyte constructs. Only the
ability to grow inside the collagen-based biomaterial was importantly reduced, even if
viability was consistently maintained. Therefore, considering implications due to FBS
presence, our choice could be a good compromise for patient's safety. The second comment
is about the validation procedure itself. GMPs Guidance gives strict indication on how to
carry on process and product validation thus minimizing contamination risks and variable
elements. However such a standardization could be difficult to apply for cells. It is known
that cell characteristics in culture are labile and subjected to modulation due non only to
culture conditions (times, culture media, supplements an scaffolds) but also to patients (age,
gender and pathology). In particular, quantification of some cell properties can become
really hard to perform, thus hampering standardization. Therefore validation of a cell-based
medicinal product, should mediate between the required “drug rules” and the intrinsic well
known cell biological variability that is impossible to eliminate. The last comment is a
consideration that cell therapy for cartilage regeneration is under vast exploration and there
are now emerging other possibilities as well as improvement in this application. Allogeneic
implantation, unexpanded chondrocytes, cell combination with new scaffolds and the use of
pre-committed or undifferentiated precursors or mesenchymal stem cells from different
sources are some examples of recent advancement in this field. In any case, Country
legislation must be applied and our system can be also assumed as a valid model for the
compliant GMPs development of other new products suitable for clinical purposes.
6. Acknowledgment
The Authors wish to thank Dr. Giovanna Desando for the technical and scientific support.
This work was supported by the grant “Progetto di Medicina Rigenerativa” from “Regione
Emilia Romagna” (Delibera di giunta n. 2233/2008).
7. References
Becerra, J., Andrades, J.A., Guerado, E., Zamora-Navas, P., Lo´pez-Puertas, J.M. & Reddi, A.
H. (2010). Articular Cartilage: Structure and Regeneration.
Tissue engineering: Part
B, Reviews,
Vol.16, No.6, (December 2010), pp. 617-627, ISSN 1937-3368
Brittberg, M., Lindahl, A., Nilsson, A., Ohlsson, C., Isaksson, O. & Peterson, L. (1994).
Treatment of deep cartilage defects in the knee with autologous chondrocyte
