Alternatives to animal serum in cell therapy manufacturing

by Alexey Bersenev on December 22, 2011 · 5 comments

in cell culture, cell product

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Because of high cost, supply limitations and safety issues, cell therapy developers have been looking for alternatives to animal serum in the last few years. There are two major directions for animal serum replacement in cell therapy:

  • defined growth factors (“synthetic” serum replacement)
  • natural human blood-derived products

I think, a great progress was made in both directions. Today, I’d like to focus on latter approach. Human-derived blood products have been validated recently in GMP-grade protocols. There are a number of comparative studies (human-derived products versus animal serum). I’ve picked few significant trends in development of animal serum replacement strategies.

Replacement of animal serum in cell therapy manufacturing:

1. Platelet lysate
Examples 1/2

2. Autologous/ allogeneic donor’s serum
Examples 1/2

3. Platelet-rich plasma
Examples 1/2

4. Cord blood serum
Example

So, I’m quite optimistic on this matter and I don’t think we will have a lot of problems with “peak serum“. What do you think?

{ 5 comments… read them below or add one }

Vasiliy December 22, 2011 at 8:56 am

I think, only autologous serum and autologous stem cells can be used in cell therapy :)

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Brandy December 26, 2011 at 4:50 pm

I enjoyed your blog, but was surprised to see that recombinant proteins were not included as a third option for animal serum replacement in cell therapy. We wrote a blog on the Cell Culture Dish highlighting the success of using recombinant human serum albumin as an alternative to knockout serum replacement. After looking at the research in this area, I find that recombinant proteins such as albumin and transferrin are more appropriate options to replacing animal and human components in stem cell culture and avoid risks and regulatory delays associated with blood-derived components. Please see the blog for more information – http://thecellculturedish.com/2010/06/an-alternative-to-knockout-serum-replacement-for-culturing-human-embryonic-stem-cells-in-animal-free-conditions-recombinant-human-serum-albumin/

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Alexey Bersenev December 26, 2011 at 5:02 pm

Brandy,
I’ve mentioned that there are two type of approaches: 1. defined growth factors and 2. natural human blood-derived products (undefined, natural mix of factors). I think recombinant proteins belong to the first group – defined factors (aka synthetic). As I wrote “Today, I’d like to focus on latter approach.”
I skip the first group of approaches, because: (1) I guess there are many of them, (2) I don’t know enough to write about it comprehensively, (3) all of them commercialized – therefore I don’t want to promote some brands and not mention the others.
I always invite people from academia and industry to write a guest post about their professional subjects or promote their brand/ product.

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Jon Rowley December 27, 2011 at 5:49 am

Alexey,

Yes, these are options, but one has to do perform a supply evaluation of each component. Once you start looking at the #s of cells required a commercial product, only scalable sources (recombinant factors) are likely to meet the supply requirements. Here is some math: Lets assume you need 2e8 cells for a single product dose (a good mid-range dose) and you have a commercial product for 100,000 (1e5) patients, that is 2e13, or 20 Trillion cells required per year for a single product. If you go to one of those papers and calculate how much human blood you would need to create one of the blood products for a single commercial cell therapy- it is staggering. Now think about supporting an industry of 10-20 products in 15 years time.

Keep up the great work on the blog, and thanks for the interest in the Peak Serum piece.

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Alexey Bersenev December 27, 2011 at 8:19 pm

Thank you Jon!
I think, this group of serum replacement products (natural blood-derived) definitely not going to supply such large scale that you’ve mentioned. The links I gave, more like proof-of-principle studies, said “it’s doable”. For large scale commercial manufacturing probably most of them not going to work. In this case, the first group (defined growth factors, recombinant proteins) will have advantage. I think, human serum and platelet-based products will play a role in autologous cell products, personalized and low scale manufacturing. At the end it will be mix of many approaches.

Btw, the trigger for this post was the very last study I’ve mentioned – potential use of cord blood serum. If you can calculate how many cord blood samples collected every day (serum is discarded during processing), you can imagine the volume of serum that could be stored or “produced”. The cryobank of few hundred thousand of CB serum samples could potentially supply large scale manufacturing. Maybe…

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