Reducing Background Noise: The Role of Exosome-Depleted FBS in Cell Culture

What are exosomes and how do they impact research?

Fetal Bovine Serum (FBS) is a vital cell culture medium supplement, rich in growth factors and essential nutrients that support cell growth and proliferation. FBS naturally contains large amounts of exosomes, extracellular vesicles released from the cells by the plasma membrane, that are associated with immune response and cell-to-cell communication. These vesicles carry various biomolecules, such as proteins, lipids, and nucleic acids, to communicate and influence other cells. As a result, exosomes in serum can interfere with the exosomes derived from the cultured cells, impacting results and data analysis.

Therefore, for those scientists evaluating exosomes of cultured cells, we recommend transitioning to using an exosome-depleted FBS or a serum-free cell culture media.  

What is exosome-depleted FBS?

Exosome-Depleted FBS is a specialized formulation of fetal bovine serum that has been processed to remove the naturally present exosomes, which can interfere with cell culture and research studies. It is specifically designed for use when isolating exosomes from cultured cells, without the complications caused by bovine exosomes.  

How is exosome-depleted FBS manufactured?

Removing endogenous bovine exosomes is done by using a proprietary ultracentrifugation process followed by ultrafiltration methods. The goal is to produce an FBS with 95% depletion of exosomes and rigorous testing to ensure the highest level of exosome depletion while retaining essential growth nutrients for cell cultures.

When should exosome-depleted FBS be used?

If you’re isolating and characterizing exosomes (or other extracellular vesicles) secreted by your cultured cells, regular FBS brings its own bovine exosomes that co-isolate and contaminate your prep. Exosome-depleted FBS has those bovine vesicles largely removed, so what you collect is predominantly from your cells, not the serum.

• When analyzing extracellular RNA, miRNA, or protein cargo in vesicles:
  Bovine exosomes carry their own miRNAs, RNAs, and proteins, which can show up in sequencing, qPCR, or proteomics and be mistaken for cell-derived signals. Depleting FBS exosomes reduces this background and makes downstream omics data interpretable.
• When studying exosome-mediated signaling or uptake:
  If you’re looking at how exosomes affect recipient cells (e.g., functional assays, signaling pathways, cell migration), bovine vesicles in standard FBS can trigger effects on their own. Exosome-depleted FBS lets you attribute functional changes to the vesicles you add or your cells secrete.
• When you need clean EV-depleted conditioned media for isolation:
  For ultracentrifugation, size-exclusion, or kit-based EV isolation from conditioned media, starting with exosome-depleted FBS reduces co-purification of serum-derived vesicles and improves purity of your final prep.
• When your readout is very sensitive to serum-derived vesicles:
  High-sensitivity assays (e.g., NGS of small RNAs, single-vesicle analysis, high-resolution flow or NTA with phenotyping) benefit from minimizing any non-cell-derived vesicles in the background.

Take note, exosome-depleted FBS is not required for routine proliferation, viability, or basic cell biology assays where exosomes aren’t the endpoint. Here standard FBS is acceptable and less expensive.

Questions? For questions or to request a quote, contact our Captivate Bio Customer Service Team today!

References

• Edgar, James R. “Q&A: What Are Exosomes, Exactly?” BMC Biology, BioMed Central, 13 June 2016.
• Raghu Kalluri Valerie S LeBleu, “The biology, function, and biomedical applications of exosomes”, Science. 2020 Feb 7;367(6478).