In laboratories, scientists grow cells outside a living organism through a process called cell culture. Some cells, especially delicate or specialized ones, are difficult to grow alone. Researchers solve this by using “feeder cells,” which are helper cells that support the growth of these target cells. Feeder cells create a nurturing environment, allowing scientists to cultivate cells that would otherwise fail to thrive in a lab setting.
How Feeder Cells Nurture Other Cells
Feeder cells nurture target cells through several mechanisms. One role is to secrete growth factors, cytokines, and other signaling molecules into the culture medium. These proteins act as chemical messengers that the target cells need to grow and divide. This constant supply of factors mimics the natural environment of cells within a body.
Feeder cells also offer a physical scaffold. They form a layer that coats the culture dish, creating an extracellular matrix for target cells to attach and spread. This physical contact is important for the survival and proliferation of many cell types, providing structural support and close-range signaling.
To prevent feeder cells from overgrowing the target cells, they are treated to stop their own division. Common methods include irradiation with gamma rays or treatment with a chemical called mitomycin C. These treatments arrest the cell cycle, so they can no longer replicate. However, they remain metabolically active, able to produce supportive factors and provide a physical matrix for a period of time.
The supportive layer also provides metabolic support by conditioning the culture environment. Feeder cells can absorb toxic byproducts and help maintain a stable pH and nutrient balance in the medium. This function acts as a biological filter, keeping the environment optimal for sensitive target cells. This layer of inactivated cells must be replaced every few days to continue supporting the culture.
Varieties of Feeder Cells
Researchers use several types of feeder cells, with the choice depending on the needs of the cells being cultured. Mouse Embryonic Fibroblasts (MEFs) have been the most widely used. Derived from mouse embryos, MEFs are effective at supporting a wide range of cells, particularly embryonic stem cells, making them a standard in many research protocols.
Another common type is the STO cell line, also derived from mouse embryonic fibroblasts. Unlike primary MEFs, which have a limited lifespan, STO cells are an established cell line that can be propagated for longer periods. This makes them a more convenient and consistent source for some research applications.
For clinical applications in humans, researchers often use human-derived feeder cells like Human Foreskin Fibroblasts (HFFs). Using human cells to support other human cells reduces the risk of introducing animal-derived molecules. This is a primary consideration for regenerative medicine, where cultured cells are intended for transplant into patients.
Applications in Scientific Discovery
Feeder cells have been important in several fields, most prominently stem cell biology. Feeder layers are a reliable method for culturing embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). They provide signals to keep these cells in a state of pluripotency, meaning they can develop into any cell type. Without this support, many stem cell lines would differentiate or fail to survive.
In virology, feeder cells are used to produce viruses for vaccines and gene therapy. Some viruses only replicate in specific host cells, and growing these on a feeder layer increases the yield of virus particles. This is useful for producing viral vectors, which are modified viruses that deliver genetic material into cells.
Cancer research also benefits from feeder cells. Co-culture systems, where cancer cells are grown with feeder cells, allow scientists to study the tumor microenvironment. This setup helps researchers understand how interactions between cancer and supportive cells contribute to tumor growth, metastasis, and drug resistance. It also enables the cultivation of patient-derived cancer cells that are otherwise difficult to grow.
The Shift Towards Feeder-Free Conditions
Despite their utility, feeder cells present challenges that have prompted a move towards feeder-free culture systems. A primary issue is the risk of biological contamination. Animal-derived feeder cells can transmit viruses or other pathogens to human cells, which is a safety concern for cells intended for clinical use.
Another limitation is the lack of consistency, as feeder cell quality can vary between batches, making results difficult to reproduce. Preparing and maintaining these cultures is also labor-intensive and time-consuming. These factors have driven the development of more defined and controlled methods.
The alternative is feeder-free culture, which replaces helper cells with a defined system. This involves using a specialized medium supplemented with purified growth factors and cytokines. Instead of a cellular layer, culture dishes are coated with purified extracellular matrix proteins like laminin or vitronectin, which mimics the physical scaffold in a controlled manner.
This shift offers advantages for research and clinical applications by eliminating contamination risks and increasing reproducibility. A chemically defined environment gives scientists greater control over the factors influencing cell behavior, leading to more reliable results. While feeder cells were foundational, the field is advancing toward these more refined and safer methods.