So how difficult will it be to re-create a medium formulation without serum? Are all of those hormones really indispensable? As it turns out, researchers have been working for a long time in creating serum-free medium formulations. The reason for this is because serum is notoriously variable from lot to lot, expensive, and can lead to mycoplasma or other contaminants. As a result, nearly all embryonic and induced pluripotent stem cell culture is performed serum-free. In the lab, I can differentiate pluripotent stem cells to terminal neuronal lineages in completely serum-free medium formulations. Other formulations have been made or are in the pipeline for other cell types. For skeletal muscle, several groups have published on the derivation or expansion of skeletal myotubes from murine or human pluripotent or myosatellite stem cells using completely serum-free conditions [
30,
31,
32]. This trend has continued with the recent publication using a serum-free method for derivation of muscle from porcine pluripotent stem cells, where the first author here is a co-founder of Memphis Meats [
33]. Indeed, while I use serum in my own published protocol for human skeletal muscle derivation [
23], expansion of skeletal muscle progenitors can be performed in serum-free conditions, specifically DMEM F12, 1% N-2 Supplement, and 1% Insulin-Transferrin-Selenium supplement. The trick seems to be via the addition of supplements or knockout serum replacements [
34] which contain only some of the essential factors found in serum, such as insulin, transferrin, selenium, putrescine, and progesterone (found in N-2 supplement). The hormones typically shamed in bovine farming include things such as recombinant bovine growth hormone and synthetic hormones such as Zeranol, Trenbolone, and Melengestrol [
35], although I divert to someone who has a better understanding as to the possible ill effects of these on human health. Thus, it’s likely clean meat will be advertised as “hormone-free” but contain indispensable hormones such as insulin. Additionally, other efforts are underway in using plant-based protein extracts known as vegetal serum or peptones [
36,
37]. In sum, while I cannot say exactly what serum-free formulations are being used by these start-ups, it is clear that it
is currently possible.