Serum-based versus serum-free clinical-grade culture of mesenchymal stromal cells – A poll

by Alexey Bersenev on May 17, 2012 · 5 comments

in cell culture, mesenchymal

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We’ve written a lot about the problem of serum use in clinical-grade cell culture. Today, I’d like to share more data and ask to express your opinion on this matter in our poll.

Use of serum and substitutes for ex vivo expansion of mesenchymal stromal cells (MSC) is a very hot topic. There are a lot of studies and protocols. Despite the fact that animal serum is not prohibited for clinical cultures, the development of commercial chemically-defined media for MSC is booming. Unfortunately, currently, there is no consensus on the optimal growth medium for MSC. Also, we are still lacking good comparative studies, which could analyze different kind of sera or serum versus artificial substitutes.

The considerations, which should be taken in account:

  • pathogen safety
  • MSC growth dynamics and quality
  • availability and cost

One of the recent studies has compared effects of different sera on adipose-derived MSC. They compared fetal calf serum (FCS), pretested fetal calf serum (FCS-Sp), human allogeneic serum (HS) or artificial serum substitute (AS):

We found that MSCs cultivated in the presence of different sera had similar global proteomic expression patterns, but comparisons of identified proteins revealed most differences in the MSCs cultivated with AS. Our results indicate that MSCs cultivated in the presence of FCS and HS display similar growth, differentiation, immunophenotypic and proteomic properties, while AS induces more profound changes in the physiology of MSCs, suggesting that further fundamental studies should be done before its introduction into clinical practice.

Sunghoon Jung comprehensively reviewed all pros and cons of defined serum-free media for clinical MSC culture. The authors currently doing a comparative study:

We have recently initiated a study to compare these commercial media along with other existing media. The media under investigation include Mesencult-XF (STEMCELL Technologies), StemPro MSC SFM Xeno-Free (Invitrogen), MSCGM-CD (Lonza), PPRF-msc6, and DMEM +10% FBS (Lonza). Our initial data show that the performance of the commercial hMSC media on the attachment and growth of primary BM-hMSCs is questionable and thus should be open to discussion.

It seem to me, that we still don’t have a good chemically-defined commercial serum substitutes/ media.

Now, I’d like to ask you: What is the best alternative to animal serum in clinical MSC expansion? Please vote in the poll:

For more information about humanized alternatives of animal serum, you can look at here.

PS: If you can not see a poll embedded in this post, follow the direct link.
PPS: If you represent a company, please refrain from obvious advertisement or promotion of your products in comments. Contact us about the promotion.

{ 5 comments… read them below or add one }

Mohan C Vemuri May 18, 2012 at 11:22 am

“Ex Vivo Expansion of Human Mesenchymal Stem Cells in Defined Serum-Free Media” is an interesting publication for the use of MSCs in cell therapy paradigms.
I like to bring up that, the authors, in particular seem to have not followed the claims and suggested protocols for certain commercial products used in this study. For example, the product, StemPro MSC SFM Xeno-Free (Invitrogen), it has been clearly indicated in the product insert and protocol recommendations that “the use of human AB serum for primary isolation and the need for priming prior to CFU-f testing”. Secondly, the authors did not mention the use of CELLstart for attachment of cells for expansion or use of TrypLE for passaging. The necessity for use of these reagents have been called out in the product protocols recommended. These reagents support the end goal of having a xenofree, defined culture system.
Mohan Vemuri


Diederik Klaassen May 21, 2012 at 6:02 pm

Hi Alex,

Not a true comment as I know you don’t want commercial information in your blog. But I would like to invite you to look at XerumFree, our fully defined, animal free replacement, GMP produced. it has been successfully tested on MSC’s at Charité in Berlin.

Best regards


yi zhang June 11, 2014 at 9:15 pm

Hi Alex
Do you know the current progress in the field of clinical grade of culture medium for MSCs or DCs? Is there any clinical grade culture available in the market which is also approved by EMA or FDA? thanks very much.


Alexey Bersenev June 14, 2014 at 2:39 pm

Unfortunately, I don’t know more than what available in public literature. According the recent review –
Only MSC-Gro (Vitro BioPharma) considered as “clinical grade”. I have to look if it cleared by FDA and if somebody is using it in clinical trials.
I’ll probably start crowdsourcing post on this topic.


Sandra Kuligowski June 16, 2014 at 9:12 am

Thermo Fisher Scientific offers a MSC serum free media as part of their Cell Therapy Systems (CTS) product line that is cleared by the FDA for the following intended use: For human ex vivo tissue and cell culture processing applications. CAUTION: Not intended for direct administration to humans or animals. I’m not aware of this being used in clinical trials currently. Feel free to contact me directly if you would like additional information.


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