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Review
.2015 Aug;21(4):345-53.
doi: 10.1089/ten.TEB.2014.0547. Epub 2015 Mar 24.

Feeder Layer Cell Actions and Applications

Affiliations
Review

Feeder Layer Cell Actions and Applications

Sara Llames et al. Tissue Eng Part B Rev.2015 Aug.

Abstract

Cultures of growth-arrested feeder cells have been used for years to promote cell proliferation, particularly with low-density inocula. Basically, feeder cells consist in a layer of cells unable to divide, which provides extracellular secretions to help another cell to proliferate. It differs from a coculture system because only one cell type is capable to proliferate. It is known that feeder cells support the growth of target cells by releasing growth factors to the culture media, but this is not the only way that feeder cells promote the growth of target cells. In this work, we discuss the different mechanisms of action of feeder cells, tackling questions as to why for some cell cultures the presence of feeder cell layers is mandatory, while in some other cases, the growth of target cells can be achieved with just a conditioned medium. Different treatments to avoid feeder cells to proliferate are revised, not only the classical treatments as mitomycin or γ-irradiation but also the not so common treatments as electric pulses or chemical fixation. Regenerative medicine has been gaining importance in recent years as a discipline that moves biomedical technology from the laboratory to the patients. In this context, human stem and pluripotent cells play an important role, but the presence of feeder cells is necessary for these progenitor cells to grow and differentiate. This review addresses recent specific applications, including those associated to the growth of embryonic and induced pluripotent stem cells. In addition, we have also dealt with safety issues, including feeder cell sources, as major factors of concern for clinical applications.

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Figures

<b>FIG. 1.</b>
FIG. 1.
Different treatments to prepare feeder layer cells.(a) Growth-arrested feeder cells. Growth arrest induced by chemicals (upper panel: such as mitomycin-C [MC] and glutaraldehyde) can be applied directly onto the culture surface followed by extensive washing. Growth arrest induced by physical methods (lower panel), such as GI, EPs, and X-ray irradiation, requires previous feeder cell trypsinization and reseeding.(b) Live feeder layer cells. In some cases, target cells may be grown in the presence of feeder cells capable of dividing. Some live feeder cells (such as human fibroblasts) may also become target cells as in the case of iPSC upon reprogramming. EPs, electric pulses; GI, γ-irradiation; iPSC, induced pluripotent stem cells. Color images available online atwww.liebertpub.com/teb
<b>FIG. 2.</b>
FIG. 2.
Feeder cell–target cell interactions.(a) Paracrine interactions. Feeder cells produce a number of growth factors and cytokines that could eventually be replaced by added recombinant proteins to the culture medium.(b) Juxtacrine and physical interactions. The presence of feeder cells is mandatory for target cells to grow, since cell–cell contact mediate juxtacrine signaling pathways and/or mechanical nest effects. Color images available online atwww.liebertpub.com/teb
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