Commercialization of stem cell secretome

by Alexey Bersenev on April 7, 2015 · 3 comments

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Stem cell secretome, collected in a form of cell culture conditioned medium (CM) or supernatant, is getting more and more attention not only from researchers, but also from industry. While growing, cells release in culture medium biologically active substances and structures, such as cytokines, growth factors, enzymes, microvesicles/ exosomes and genetic material. Therapeutic value of stem cell CM was demonstrated in many studies, reviewed here. The first clinical trials, assessing CM have been started. The results of the first clinical studies were recently published.

Theoretically, CM could be great pharmaceutical/ medicinal product. Compare to cells, CM could be easily biopreserved, sterilized, packaged and stored. If CM as good as cells therapeutically, it could outcompete some cell-based therapies on the market. The big question to me here is the following: How conditioned media should be regulated?

On the one hand, stem cell CM contains highly potent biological substances and could be easily manufactured as a drug. On the other hand, it’s very hard, if not impossible, to define complete biochemical composition of CM, measure activity of the main component, define and standardize therapeutic doses. In any given time, secretome of single stem cell culture could change dramatically (every hour or every day). Secretome of stem cell cultures from 2 different individuals will not be identical.

Some CM products developers chose to follow regulatory path for drugs – submit application for clinical trials and report results. But this is not a path, which was chosen by many companies, commercializing CM. Some examples:
1. Recently, US-based stem cell therapeutic company Stemedica announced worldwide manufacturing license of VitriLife to their subsidiary StemProtein. VitriLife is a stem cell CM, stabilized by Preservation by Vaporization (PBV) technology. The product is vaporized and could be stored at ambient temperature for 2 or more years. It comes in all possible forms:

Stemedica products currently in development include eye drops, inhalable dry powders, wound dressings, injectable (parenteral) solutions, nose drops, sublingual tablets and a variety of skincare and dental product

PBV preserves a mixture of macromolecules that are secreted by stem cells in culture. The thermostable mixture contains sensitive biologicals, such as cytokines, chemokines, growth factors, matricellular proteins, enzymes, mRNAs and microRNAs.

They have plans to commercialize it for many conditions – from skin problems to Alzheimer’s disease. No information about regulatory status – it looks like self-launch.
2. Stem cell CM in cosmetic products has been commercialized and sold all over the world. Just a few examples here:
Regenica creme by SkinMedica:

Human Fibroblast Serum Free Conditioned Media is the most dominant active here. These growth factors (or cytokines) are naturally occurring proteins that stimulate cells to go forth and multiply and differentiate themselves from other cells. Growth factors bind to specific receptors on the cell surfaces.

LifeLine skin care – daughter company of International Stem Cell Corporation:

Scientists at Lifeline Skin Care discovered that human non-embryonic stem cell extracts can help renew skin — by replacing old cells with healthy new ones. These stem cell extracts help stimulate your own skin’s abilities to repair itself. And Lifeline anti-aging stem cell serums were born.

Blue Horizon:

Our skin care is derived from what stem cell scientists call a conditioned medium. Here, human stem cells from placentas and umbilical cords condition the culture medium by releasing cytokines and other skin regenerating proteins that become available for skin repair. We stabilize the liberated cytokines, rendering them safe and accessible for aesthetic skin improvement. The conditioned medium is the base for our stem cell skin care products.

Celprogen introduces stem cell derived CM:

This stem cell derived conditioned media has been utilized in skin care products for over a decade. The adult stem cell derived conditioned media comprises approximately 90% active ingredient in regenerative skin care products for topical use. The adult adipose and mesenchymal derived stem cell conditioned media, is serum free and devoid of all animal components. Celprogen manufactures stem cell derived conditioned media in 2,000L-10,000L batch sizes

Despite the fact that stem cell CM has been on a market (as component of skin creams) for a decade, FDA only recently weighted on it. Agency considers “stem cell CM” activity in skin creams as a drug. The recent warning letter to Cell Vitals clearly reflects FDA’s position:

…your products “ReLuma Advanced Stem Cell Facial Moisturizer,” “ReLuma Skin Illuminating Stem Cell Anti-Aging Cleanser,” and “ReLuma Stem Cell Eye Cream” appear to be promoted for uses that cause these products to be drugs under section 201(g)(1)(B) and/or 201(g)(1)(C) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 321(g)(1)(B) and § 321(g)(1)(C)]. The claims on your website indicate that the products are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or articles intended to affect the structure or any function of the human body, rendering them drugs under the Act. The marketing of these products with claims evidencing these intended uses violates the Act.

But what if company will use CM for therapies without marketing claims on a web-site? Will FDA react?

I’d like to ask you – What do you think about stem cell secretome commercialization? How should it be regulated? Should we leave alone skin creams and regulate only iv infusions for serious illnesses?

{ 3 comments… read them below or add one }

Ray April 8, 2015 at 4:26 pm

Interesting write-up. I was using conditioned media decades ago when I was culturing pancreatic stem cells. I knew it made a difference in their growth/differentiation, but I never really had the time to expand those observations to other cell types. To think, if the company (now bankrupt) had thought to dry it down and sell it…

I wish it were as simple as “If we don’t tell anyone what to use it for, the FDA won’t stop us”. I suppose you could sell it for some other purpose, and have some physician prescribe it for off label. Nutritional supplement?

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Tony Simula April 15, 2015 at 7:50 pm

Trying to develop a CM based product as a therapeutic would be a regulatory nightmare. You would need to characterise all the active components in that mixture and demonstrate that each, separately, is safe and efficacious. Let alone trying to establish specs on its purity/impurity profile. Batch to batch variability would also be an issue. This was tried years ago with a similar product based on a cheese whey extract that contained many growth factors. The regulatory hurdles were simply too high to try to get it approved by the FDA/EMA/TGA.

As for avoiding the regulatory path, I wouldn’t go there. Some of the factors are implicated in tumorigenesis and we just don’t know enough about what they will do to cells over a long period of exposure, assuming people will apply these creams on a regular basis.

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Christian Hunter October 21, 2015 at 8:56 pm

What would you scientists advise us curious civilians to do? It would seem there’s little debate that CM can be efficacious in a variety of applications, however, this post, as well the comments, suggest that regulated CM products won’t likely appear anytime soon (not broadly anyway) owing to CM’s uniquely challenging profile for FDA approval. There’s also concerns about potential toxicity as a tumorigenic.

So I’d like to know, are there any CM products (of those listed above or elsewhere) that you yourselves would consider using or recommending to others?

Thanks in advance for your consideration and time.

Christian Hunter
Austin, TX

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