Declining productivity in long-term CHO cultivation, why!? - (Oct/10/2012 )

I apologize if this I am writing under wrong topic, but this is concerning mammalian cell culture in small scale STR's.

In long-term continuous cultivations (or shorter fed-batch cultivations with aged cells) I have observed a significant decrease in productivity when using mammalian cells.

I am referring to cells which have been continuously cultivated in a bioreactor for at least 1 month, or cells that have been passaged for at least 2 months and then inoculated into a bioreactor.

I have also observed a significant increase in cell growth rate.

How does cell age affect productivity and cell growth rate?

thank you

Have a look for this paper: Mortality and Immortality at the Cellular Level. A Review. L. Hayflick, 1997.

bob1 on Wed Oct 10 20:12:54 2012 said:

Yes, I have read some of Hayflick's work and I accept his argumentation about molecular disorder, longevity and replicometer. However, I still dont feel that I can explain the fact that the growth rate increased significantly with cell age. I believe I observed the "hayflick limit" when cultivation the oldest cells, but I do not understand the high cell growth rate prior to that limit.

besides cells reaching the Hayflick limit, you will also be getting a sub population of (a) cell(s) that have transformed - hence the growth rate. This event is rare, about 1 in 10^7 cells will transform.