Do you know that fat stem cells and bone marrow stem cells are really, really different? | BareFacedTruth.com

Do you know that fat stem cells and bone marrow stem cells are really, really different?

Some things seem like they should be the same, but in fact are really, really different.  You know, like those celebrity pictures posted online or in tabloids where you see the same famous person with and without makeup.  So it is in the field of human stem cells. There are many different types of stem cells – but they don’t all have the same jobs in our bodies, and don’t look the same (biochemically and functionally). There are difference that are minor, and then there are differences that are major and fundamental to the rationale of why we employ them to make growth factors for skin rejuvenating purposes. This post is about such differences.

It’s no secret to readers here that DrJohn and DrGeorge have day jobs as stem cell researchers, both in the lab and the clinic, and have developed skincare products whose hero ingredients (human growth factors, cytokines, mRNAs,miRNAs, etc) derive from stem cells on permanent loan from bone marrow of young adult humans. Wearing physician/scientist/business hats has proved both interesting and challenging. Interesting in how so few people have even a rudimentary understanding of stem cell science; challenging in how best to educate people so they can grasp it.

Add to that more than a decade of nearly criminal misuse of the words “stem cell” in cosmetic advertising, and the mountain we have had to climb is both steep and high. After launching our company, like Apple Computer and Hewlett Packard, self-funded guys in a garage (true story), we had to be the tortoise, not the hare.

We’ve crawled, we’ve walked, and now we’re running. Our products were recently adopted for use and resale at one of America’s most prestigious hospital systems, a clinic listed year after year among America’s top 10 hospitals by CNN and US News & World Report. Educating their physicians and nurses about the differences between stem calls and the bio-signals they produce was key to landing this account.

Doctors can’t know everything, but surprisingly few know anything about bio-signals in skincare.

When our skincare products were first exhibited at a medical trade show, it was obvious that very few physicians are knowledgeable about cytokines and growth factors. Doctors know best what they do on a daily basis, and unless they are interested in learning about stem cells and bio-signals, they remain uninformed, even dermatologists and plastic surgeons. What surprised us most was the number of times we were told “you need to speak with my nurse” or “talk to my office manager” about this topic.

In the typical medical practice, prescription medications, including new drug development, are under the purview of physicians, non-prescription topical products, not nearly as much. It seems most physicians rely on their female office staff to make recommendations about what skincare products they should offer their patient clientele. That appears to be changing. As clinical evidence supporting new uses for bio-signals evolves, more physicians are paying attention.

“You say growth factors and cytokines can improve my procedure outcomes?”

Understandably, physician interest dramatically increased with the development of bio-signal products that focus on procedure outcomes. No surprise there.  Aesthetic physicians make most of their money by providing procedures. Add to that the growing trend for less invasive procedures, laser resurfacing and dermal needling instead of surgical excision of tissue, and doctors seem to be all ears. Again, education is key. Seeing 40% faster post-laser healing, and dermal needling results that rival much more invasive procedures, more and more physicians are taking notice of the value of bio-signals in their aesthetic practice. Your humble BFT servants are honored to be leading the charge.

Like other things in life, not all bio-signals are created equal.

Whether within the body or in a laboratory flask, growth factors and cytokines patterns are determined by the genetic material within the cells that produce them.  To intelligently employ bio-signaling molecules in one’s medical practice (or one’s home skincare regimen), there should be familiarity with the significant differences among the bio-signals patterns produced by adipose (fat) stem cells and bone marrow mesenchymal stem cells, and for completeness, fibroblasts. These are the three most commonly cultured cells used to produce growth factors and cytokines for skincare products.

Their major characteristics:

Adipose stem cells are most proficient at creating more fat cells, and at producing pro-inflammatory cytokine patterns. In that regard, they are like fat cells throughout the body, especially those within fat deposits in the mesentery and omentum of the abdominal cavity. Fat is known to be an inflammatory “organ”, continuously secreting pro-inflammatory bio-signals. Inflammation is well established as a pro-aging in all tissues, particularly the skin.

Fibroblasts are the source of collagen, elastin, and matrix (glycosaminoglycans and proteoglycans, including hyaluronic acid.)  They are the major population of cells within the dermis and very easy to culture. They represent the first generation of cell cultures for skincare but in fact are a very poor choice if the objective is to produce growth factors and cytokines. In healing, they are the corporals, taking their orders to proliferate and produce collagen, elastin, and matrix from the commanders-in-chief of healing, bone marrow mesenchymal stem cells. Fibroblasts are extremely poor producers of bio-signals.

Bone marrow stem cells are the cells in charge of healing in all tissues, not just the skin. Their role in healing was first thought to be a result of their ability to differentiate into other cell types e.g. muscle, bone, cartilage, nerve, etc. We now know that cellular differentiation is only a small part of the role they play. Their other, much more important role, is to act as smart local “drugstores”, secreting the growth factors and cytokines that influence the behavior of nearby cells. Far from stationary within the bone marrow, they migrate into the blood stream where they gain access to the entire body. Radioactive tagging in animal models demonstrates that these remarkable cells can participate in healing, then return to the bone marrow to later again be called to duty.

As discussed elsewhere on BFT, aging skin results from decades of accumulated micro-injuries, and from chronic smoldering inflammation, which is actually a major contributor to aging in all tissues. Our work focuses on bone marrow stem cells because of their preeminent physiologic role in subduing inflammation and as command and control of tissue healing throughout the body.

Graphics clarify the difference.

Note the first bio-signal pattern below, the growth factor/cytokine pattern produced by bone marrow mesenchymal stem cells. It is highly ANTI-inflammatory. Contrast it with the next image, the highly PRO-inflammatory pattern obtained from cultures of adipose (fat) stem cells.

If one agrees that inflammation, especially chronic inflammation, is pro-aging, it seems prudent to us to apply topical products that contain anti-inflammatory bio-signal patterns, particularly if one is adopting a product as part of a daily skincare regimen. While not our choice for daily skincare, we do see possible value for the pro-inflammatory output of adipose stem cells for specific episodic applications. We are investigating one particular indication and will report our findings.

Below is a comparative graph of important growth factors and cytokines produced by cultures of fibroblasts (white bars) vs bone marrow stem cells (blue bars.) The dramatic difference is obvious; bone marrow stem cells produce many, many times the concentration of bio-signals as is produced by fibroblasts. The degree of greater production can be seen in the table below the graph.

Comparative Superior Bio-signal Output of Bone Marrow Stem Cells v Fibroblasts

Bone Marrow Stem Cell Product 15 to 49 times the concentration of important bio-signals.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

“All stem cells are definitely not created equal.” Peer reviewed research into fat and bone marrow stem cells demonstrates the dramatically different effects their bio-signal patterns have on physiology and cellular behavior. Some of the summaries below are from abstracts published only a few months ago.

 

The obesity cancer paradigm: exploration of the interactions and crosstalk with adipose stem cells   Stem Cells 02/2015

The increased morbidity and mortality of obesity-associated cancers have been attributed to higher levels of hormones, adipokines, and cytokines secreted by the adipose tissue. The increased amount of adipose tissue also results in higher numbers of adipose stromal/stem cells (ASCs). These ASCs have been shown to impact cancer progression directly through several mechanisms, including the increased recruitment of ASCs to the tumor site and increased production of cytokines and growth factors by ASCs and other cells within the tumor stroma.

Adipose derived stem cell isolated from omentum: A novel source of chemokines for ovarian cancer growth Journal of Cancer Research and Therapeutics 01/2014

Omental adipose tissue may play crucial roles for tumor promotion through the expression of tumor promoting chemokines. Accordingly, tumor surrounding adipose tissue may be a novel target for immunotherapy of cancer.

Mammary Adipose Derived Stem Cells In BRCA-Related Breast Cancers                                                  Plastic and Reconstructive Surgery 05/2015

…adipose stem cells (ASCs) are further implicated in their secretion of harmful, pro-inflammatory cytokines to contribute negatively to the local tumor micro-environment. [….] Aggressive epithelial breast cancers are dependent on the local stromal environment that creates a favorable field for tumor growth and invasion, including a chronic pro-inflammatory cytokine profile.

Breast cancer: Adipose tissue, a bulky neighbor causing trouble                                                                           BioMed Central 05/2015

We now know the fat reservoir has very active functions: it produces and secretes many biomolecules such as hormones, growth factors and pro-inflammatory cytokines, molecules named adipokines. Numerous studies have shown that adipocytes and their progenitors promote breast cancer aggressiveness by stimulating proliferation and, especially, invasion by secreting proteases and pro-inflammatory cytokines.

Human omental-derived adipose stem cells increase ovarian cancer proliferation, migration, and chemoresistance    Plos One 12/2013

Adipose tissue contains a population of multipotent adipose stem cells (ASCs) that form tumor stroma and can promote tumor progression. [….]ASCs derived from the human omentum can promote ovarian cancer proliferation, migration, chemoresistance and radiation resistance in-vitro.

Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion                Brazilian Journal of Medical and Biological Research  Sept 2013

To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were co-cultured with pancreatic cancer cells. [….] conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells.

Bone marrow mesenchymal stem cells suppress metastatic tumor development in mouse by modulating immune system.  Stem Cell Res Ther. Mar 2015

Our results demonstrated that BMSCs treatment caused a delayed tumor growth and a prolonged survival in both tumor models. […] in vivo and in vitro results showed that BMSCs have a systemic suppressive effect

Paracrine effects of mesenchymal stem cells induce senescence and differentiation             of glioblastoma stem-like cells. Cell Transplant 2015 March

Glioblastoma multiforme (GBM) displays high resistance to radiation and chemotherapy […] possible anti-tumor effects of the secreted factors from human MSCs on four GBM cell lines was examined[…] Conditioned media from bone marrow and umbilical cord-derived MSCs (MSC-CM) was found to mediate GBM cell cycle arrest. […]Findings support the notion that BM-MSCs posses an intrinsic ability to inhibit cell cycle and induce senescence and differentiation of GBM cell lines.

A comparison of adipose and bone marrow-derived mesenchymal stem cell secreted factors in the treatment of systemic inflammation  Journal of Inflammation Nov 2011

Conditioned media from adipose and bone marrow stem cell cultures was injected into animals with septic shock and systemic inflammation. The bone marrow stem cell condition media counteracted the inflammatory cytokines, resulting in improved animal survival. Adipose stem cell condition media increased the inflammatory state, resulted in worsening of the animals’ condition and more deaths.

 

 

30 Comments

  1. Curious says:

    Wow! I am going to have to revamp my product wishlist by a lot. Sigh. Otherwise. Thanks for providing this wealth of information!

  2. Curious says:

    Ok, so now I am eliminating all of the products that have adipose stem cells in them I have two questions. In light of the info above:

    “Conditioned media from bone marrow and umbilical cord-derived MSCs (MSC-CM) was found to mediate GBM cell cycle arrest”

    If umbilical cord stem cells are ok to use…are placenta stem cell products ok to use as well?
    Also how would a product that lists ‘human tissue cultured media’ be classified? Is this the same as ‘stem cell cultured media’? Just different wording?

  3. Curious says:

    I also have some sample kits of skincare products that say ‘human stem cell culture media’.

    I guess what am I asking is what can one infer from the following phrases:

    human cell culture media
    human tissue culture media
    stem cell culture media
    stem cell culture fluid

    I am comparing the labels of the products that I have bought or am looking to purchase and test. None of these products, and they are several by different companies- say whether they use adipose (I got rid of the ones that did) or bone marrow or whatever they are using at all. They all use one of the phrases listed above.

    • drjohn says:

      Go Curious!

      They are telling you the source, but not the niche. Maybe the product makers themselves don’t know how important the differences are! Scary thought, but we have found a dearth of actual =scientists in this realm. That’s why DrGeorge wrote this post – its important to know the difference! If you send us the product names we will find out for you and post it here for all.

    • Jon Bon Jovi says:

      All those phrases just mean the same thing: exosomes.

      They take a stem cell and culture it. Then then take the medium it was in and sell it. Perhaps the stem cells from whence these companies derived the exosomes were not human? But plant, or other animal?

      • drgeorge says:

        Not sure what “phrases” you are referring to, but your statement about culturing stem cells and selling the medium as “exosomes” is off the mark. Although some companies have been pulling this charade for years, claiming their products contain exosomes simply because it contains culture media. Any multi-ingredient formulation containing culture media sold as an emulsion DOES NOT CONTAIN intact exosomes. Exosomes are delicate and easily lysed by mechanical and “solvent” actions on their lipid enveloping membranes.

        True exosome products do start with culture media which must undergo extensive steps to concentrate the exosomes in order to claim it is an “exosome” product. Then the issue of storage and stabilization is hugely important. Two ways can be used: freezing and shipping as frozen product at very low temperatures, or lypholizing (freeze-drying under strictly controlled conditions) which makes possible storage under refrigeration until reconstitution with appropriate diluent.

  4. Curious says:

    Thank you Dr. John for the response and Dr. George for the post!

    The first line is called Ohui. I think they are manufactured by LG and sold in Korea. I couldn’t find their main site in English so I had to find a translator. The official name of the product line is: Ohui The First Cell Revolution. I have the emulsion, soft cream, and the geniture cream from the line. Here are the links I could find.

    Ohui emulsion: http://www.microsofttranslator.com/bv.aspx?from=ko&to=en&a=http%3A%2F%2Fwww.ohui.co.kr%2Fproduct%2Fdetail.jsp%3Fpid%3DACM04283%26cid1%3D2%26cid2%3DA

    Ohui soft cream: http://www.microsofttranslator.com/bv.aspx?from=ko&to=en&a=http%3A%2F%2Fwww.ohui.co.kr%2Fproduct%2Fdetail.jsp%3Fpid%3DACM08442%26cid1%3D2%26cid2%3DA

    Ohui geniture cream: http://www.microsofttranslator.com/bv.aspx?from=ko&to=en&a=http%3A%2F%2Fwww.ohui.co.kr%2Fproduct%2Fdetail.jsp%3Fpid%3DACM06917%26cid1%3D2%26cid2%3DA

    Ohui uses the phrase stem cell culture fluid and I have seen some ads on the internet for their products that say stem cell culture media.

    Now this is a line that I was thinking abut buying. They have two products- a serum and a cream. This is another Korean company called Its Skin. I couldn’t find a main website for them at all, but the products are sold through resellers. Here are the links:

    Its Skin Prestige Cell Concentrated Serum: http://en.koreadepart.com/item/1424842490/its-skin-prestige-cell-concentrated-serum

    Its Skin Prestige Cell Concentrated Cream: http://en.koreadepart.com/item/1424845995/its-skin-prestige-cell-concentrated-cream

    Its Skin uses the phrases human stem cell conditioned media and human tissue culture media.

    Those are the ones that state that they have human stem cells in them.

    • drjohn says:

      I think the English translation should be spelled Oh Hooey!

      Ohui claimes their cream has: “embryo derived stem cell culture medium called the CHA-HSCMTM which offers superior efficiency and approved by the Korean Drug and Food Administration” which is true means they use embryonic stem cells. This means using aborted fetuses or other such tissues. And such a shame that a baby had to die for your skin, because it was totally unneccessary – we now know that stem cells from adults have all the same potential benefits.

      The they have another one called Ohui #1 cell power, which has nothing to do with cell cultures of humans. It contains proteins derived rom recombinant technology (grown in e-coli bacteria). Calling it “cell power” is a marketing ploy. Only cells used were the bacteria. Here is the very very long list of ingredients:

      Water
      Sodium Hyaluronate
      Dipropylene glycol
      SD Alcohol 40B
      Glycereth-26
      Glycerin
      Mistletoe
      Lactobacillus/soybean Ferment Extract
      Niacinamide
      Poncirus Trifoliata Fruit Extract
      1,2-Hexanediol
      Biosaccharide Gum-1
      Methylpropanediol
      Polyglutamic Acid
      Methyl Gluceth-20
      Spiraea Ulmaria Extract
      Polymethylsilsesquioxane
      Phenoxyethanol
      Chlorphenesin
      Caprylyl Glycol
      Glycosphingolipids
      Phospholipids
      Cholesterol
      Hydroxyproline
      Polyquaternium-51
      Lauryl Dimethicone/
      polyglycerin-3 Crosspolymer
      Cetearyl Alcohol
      Surfactant
      Rhizobian Gum
      Tromethamine
      pH Adjusters
      Acrylates/
      C10-30 alkyl acrylate crosspolymer
      Methoxycinnamidopropyl Hydroxysultaine
      Butylene Glycol
      Hydrogenated lecithin
      Oligopeptide-2
      Oligopeptide-10
      Fragrance
      Citrus aurantium dulcis
      Trisodium EDTA
      Lecithin
      Sodium phosphate
      Sodium chloride
      Disodium EDTA
      Phosphate Buffered Saline
      Glutamic Acid
      Histidine
      Threonine
      Glucose
      Fructose
      Creatine
      Urea
      Anti-inflammatory
      Calcium chloride
      Magnesium chloride
      Serum albumin
      Hydrolyzed soy protein
      Hydrolyzed wheat protein
      Xanthan Gum
      Geranium Maculatum Oil
      Pinus pinaster
      Paeonia Lactiflora Root Extract
      Algae Extract
      saccharomyces/imperata cylindrical root ferment extract no matched results
      rh-polypeptide-5
      rh-polypeptide-1.sh-oligopeptide-10
      rh-polypeptide-15
      sh-polypeptide-18
      sh-polypeptide-43
      rh-polypeptide-7
      asparagines
      glutamine glycine
      tripeptide-1.portulaca oleracea extract
      hydrolyzeo candida
      saitoana extract
      polydatin

  5. Curious says:

    Another product that I was thinking of buying, but eliminated was the RubyCell line. They say that use advanced human adipose stem cells.

    http://www.aphrozoneusa.com/standard/03product/productList.do

    http://weducoop.tradekorea.com/product.do

    Their befores and afters are really amazing though. 🙂

    https://www.youtube.com/watch?v=sN1-pGJr7bE

    • drjohn says:

      Never, I repeat never, believe before/after as your prime evidence for efficacy. Too many ways to manipulate.

    • drjohn says:

      Adipose stem cell products are popular in Korea and here in the U.S. The cells are easy to obtain (byproducts of liposuction from overweight 50’ish women), and grow quickly. problem is that there are no markers that tell you the difference between fat stem cells and pre-adipocytes (non-stem precursors to fat cells). The latter produce abundant adipokines – the biosignals associated with various cancers and inflammatory conditions.

      RubyCell is one of those. Contains 5% of human advanced adipose-derived stem cell protein extract. which is rather weak. You can buy 1n 18-day supply on Amazon for $430. Outrageous. That’s more than 5x the cost of AnteAge which delivers a far more concentrated solution of a truly regenerative anti-inflammatory cytokine and growth factor profile. What’s wrong with this picture??

      • Real Stem Cell Scientist says:

        I find it fundamentally wrong for you guys to be claiming to be stem cell experts when you’re not, and worse, acting like you are unbiased and just trying to help the average consumer. Nothing could be farther from the truth. … 5+ years ago, there wasn’t a lot of stem cell scientists in the world, and guys like you have gone unchecked, but now you’re bringing down the credibility of the whole industry and making a mockery of real science. EDITED FOR REASONS DISCUSSED BELOW

        • drjohn says:

          This person, claiming to be a “real stem cell scientist” wants to challenge us on various matters, including the utility of adipose derived stem cells in dermatology and aesthetics. So it appears he wants us to believe that he has superior credentials, and thus is the superior judge of all things stem cell. Now, I did not publish the rest of the comment because I find this sniping to be both unprofessional and cowardly. If you have an opposing viewpoint, and want to engage in reasoned scientific debate, you do not do so by being anonymous and making unsupportable claims. We tell you who we are, and our biases, so why don’t you do the same? Don’t argue for your viewpoint using ad hominems (you know what that means, I presume) because that is the worst kind of useless discourse that neither proves your point nor affords you any credibility whatsoever.

          So tell us us who you are, and what are your qualifications, and why you think you are better qualified than we are, and then we will publish your argument alongside our own. Tell us your degrees, training, your affiliated institutions, your commercial interests, who is on your advisory boards, and the stem cell / regenerative medicine conferences in which you regularly participate. Where is your lab? We promise to lay ours all out, with proof if needed, if you do. I suspect you do not really know our qualifications, and they may even surprise you.

          Collegial debate of opposing viewpoints in science is healthy. Trolling the internet is not – it is merely juvenile and small minded. Show us who you are, and then let the real debate begin.

  6. Curious says:

    Wow Dr. John.

    Thank you so much for the information! I am shocked speechless by the Ohui. I definitely did not see that listed. Wow.

    Re: Ruby Cell – I had no idea that the concentration was weak. I think they also have a 20% ampoule, but regardless, if it causes inflammation – then I don’t want it.

    Again, I want to thank you so much for the response and analysis. 🙂

  7. Curious says:

    Hello,

    I found out some more information on the Its Skin Prestige Cell Products! They are manufactured by JNC International. They have a website, but it is all in Korean. I had to use a translator.

    Its Skin Prestige Cell Concentrated Serum: http://www.microsofttranslator.com/bv.aspx?from=ko&to=en&a=http%3A%2F%2Fwww.itsskin.com%2Fshop%2Fview.asp%3FP_IDX%3D2320

    Its Skin Prestige Cell Concentrated Cream: http://www.microsofttranslator.com/bv.aspx?from=ko&to=en&a=http%3A%2F%2Fwww.itsskin.com%2Fshop%2Fview.asp%3FP_IDX%3D2321

    Can you determine what kind of cells they are using?

    • drjohn says:

      They don’t tell you what tissue the tissue culture is based on. Maybe because they don’t want you to know. This is another Korean company with a line of snail snot products.

  8. Victor says:

    Dear Dr. John,

    Is there any way you could shed some light about Embrionic Stem Cells? Are the more similar to AD-MSC or to BM-MSC, with regards to the cytokines they produce? If you are to inject stem cells to promote anti-fibrotic process to repair scar-tisse and dissolve it, would you inject only stem cells, or would you also inject cytokines along with them?

    Thanks a lot!

    • drjohn says:

      Excellent question, Victor. I’ll start with some basics, but need to do a whole post to do the topic justice. Now, most people have heard of embryonic stem cells and adult stem cells. We used to think(5 years ago) that embryonic stem cells had great advantages over adult stem cells in terms of regenerative capabilities. That distinction is not nearly as important as we used to think – and we now know that differentiation is a two way street. What this means is that stem cells can not only differentiate into more mature (tissue specific) cells, but they can also de-differentiate into more “primitive” cells, as least in terms of their secretome (chemicals they produce to coordinate their activities and to tell other cells what to do). And to some extent into their “potency” (ability to make more kinds of cells). At the same time, we have also discovered that the benefits of stem cells (e.g. to stop a heart attack, etc) are about 95% based on these chemicals, and maybe 5% based on differentiation. What does this mean for embryonic stem cells (primitive to start with)? Fewer reasons to use them, in contrast to post-embryonic or adult stem cells for most purposes. Why is this important? Embryonic stem cells are burdened my ethical issues. Regardless of where you are on the spectrum of when life begins, at least 1/2 of the US population, and a larger percent worldwide, believe that destroying embryos to get stem cells is morally unacceptable. And even if you fall on the side that it is morally OK, you then have to deal with the fact that human embryonic stem cells (hESC) can produce tumors (teratomas) that adult stem cells (hASC) will not. As a result of all this, we are seeing fewer regenerative medicine applications with hESC vs hASC than in the past.

      Victor then asks about AD-MSC vs BM-MSC. Both of these belong to the class of stem cell called MSC or mesenchymal stem cell. This is the largest class of stem cell in the human body, and is present in many “niches” (typically this means the tissue they reside in and the function they serve in physiology/biochemistry and generation/regeneration/repair). AD-MSC means adipose tissue stem cells. and BM-MSC refers to s special class of bone marrow resident stem cells. The latter are unique in that while they reside in bone marrow, they are actually not fixed, but mobile, traveling by bloodstream to effect repair & regeneration throughout the body. Now, the function of AD-MSC (also called fat stem cells) is to create more fat cells – either to replace those that die or to accommodate more body fat. Body fat as an organ is unique in that it can keep growing as long as dietary energy is present in excess. There are lots of stem cells in fat, which means that lots of fat cells can be made. Fat cells store energy, but they also secrete hormones like leptin (called ). It turns out that fat stem cells grown in culture behave a lot like fat cells in that they create such hormones. This may reflect the fact that it is hard to separate the fat stem cells from fat precursor cells – they don’t lose their “stemness” markers all that quickly as they begin to differentiate. Now, the problem with this is that those adipokines are inflammatory. Inflammation can be useful to get healing going, e.g. in a non-healing diabetic ulcer. But soon it becomes the enemy and leads to fibrosis and scarring. And leptin is also know to stimulate certain hormone sensitive cancers. Fat stem cells are not designed to regenerate organs other than fat cells. So they are not our first choice for regeneration – at least not for skin – but they are popular because they are cheap. Byproducts of liposuction. But liposuctioned fat stem cells are typically from 50+ year old people. Not just adult, but older adult. Stem cells do change with age. So, another reason we tend to avoid these stem cells for skin. Except maybe for scalp (hair regeneration) where there is little concern about the quality of epithelium as long as hair grows to cover it.

      So, we have talked about embryonic stem cells, and adult stem cells, focusing on two niches, fat and bone marrow. I should mention that there is another source for stem cells that is neither – but is from very young humans and their moms. Placental stem cells, and umbilical cord blood stem cells. They are similar in terms of secretome (cytokines produced). They are not embryonic and there is no danger of teratomas, and no embryos are killed. They are waste tissue and easily obtained. We know less about these that BM-MSC’s. They are younger so that may confer some advantages. They are also easy to harvest, and no pain is involved. My wife corrects me – there is that pain of childbirth. More on these in that upcoming post.

      Victors other question is about injecting stem cells vs stem cells plus cytokines (derived from stem cells in culture, or recombinant technology). Both are fine. The reason you may want to supplement stem cells with particular cytokines is for the reasons we discussed above. For instance, the most potent anti-fibrotic, anti-scar cytokine is TGF-beta3. All stem cells make it, but more primitive stem cells make more. You don’t want to use fetal stem cells, so you have other strategies available. One is to add more TGF-beta3 when you infuse stem cells. In fact, controlling the stem cell cytokine is the ultimate in regenerative therapeutics. Not just any old stem cell, but the right one for the job. For greater control, grow them in culture, talk to them in their language (cytokines), and get them to produce more of the desired cytokines and growth factors. We, in fact, use both strategies in our own product development.

      Hope this helps. Will get to a new post on all this soon.

    • drgeorge says:

      Drjohn provided a in-depth answer so this will be very brief.

      Studies have compared stem cell populations from different tissues to embryonic stem cells, looking for similarities in cell markers and bio-signal production. Bone marrow mesenchymal stem cells display the most similarities.

      If combating fibrosis is the therapeutic goal of injections, it seems prudent to stay away from patterns of bio-signals that are clearly pro-inflammatory, something well documented for adipose derived stem cells. A better choice would be conditioned media (the nutrient broth after cells are culture in the laboratory), or stem cells have proven anti-inflammatory effect.

      Not having experience with the condition for which you are seeking treatment, we must defer to your specialist consultants. Do insist that they provide you with their evidence of efficacy and safety before agreeing to be treated…unless you elect to be part of a study under being undertaken with IRB (Independent Review Board) oversight. Good luck.

  9. Victor says:

    Dear Dr John and Dr George,

    First of all I want to thank you for the great, informative and clear responses from you both. It feels really good to be able to talk about these complex issues with caring, knowledgable and passionate doctors like you both. Thanks a lot.

    I do understand now a lot better the differences between embryonic stem cells and the other adult stem cells. Very clear and easy to understand. I can see why nowadays there is even fewer reasons to use embryonic than several years ago.

    I learnt about the importance of cytokines from your texts and articles, and now I see that reinforced. The question about whether or not to use cytokines along with stem cells came from the knowledge that the stem cells already produce them, so why the need to (re)use them, but I now understand that it might be good to supplement it depending on the condition, like the TGF-beta3 for anti-fibrotic purposes.

    Being a complicated world, this one of the stem cells, I am learning a lot, and enjoying the journey thanks to the way you explain it.

    Based on your explanations I think that for anti-fibrotic purposes Placental stem cells will work better than ADSC. And I will definitely ask for evidence of efficacy and safety.

    Thanks again for your time and words. Much appreciated.

  10. Paul says:

    Hello,
    that advise you to clean the sensitive face ?

    • drjohn says:

      Water works well. And it avoids so many potential irritants, and does not disrupt the skin’s natural protective barrier.

  11. Katherine says:

    Could you list the entire ingredients in your products?

  12. Helen says:

    Is Anteage cosmetics safe to use?

    • drgeorge says:

      Not only safe, exceedingly so, Helen.

      Over the past six years, many, many thousands of units of our Serum & Accelerator, and Microneedling Solution have been sold under the AnteAGE and AnteAGE MD brands, as well as under a half-dozen other private label brands that are sold in North America and Asia. To date, we are not aware of a single serious adverse event with any product we produce.

      Because there are more active ingredients in our Serum & Accelerator products than any other skincare system, it may take a few days or so to become accustomed to ingredients such as retinol. The Microneedling Solution enjoys a pristine history of being exceptionally well tolerated.

      The effectiveness of our products in helping manage inflammation and promoting healing is why some of the busiest laser clinics use our products to reduce “downtime” by up to 40% and reduce chances of PIH (post inflammatory inflammation). Our Microneedling Solution (under private label arrangements) is marketed by several of the largest medical aesthetic equipment manufacturers. To date, we are unaware of any adverse events.

  13. Ellen says:

    Hello and thank you for all of the very informative information I have learned through your website.
    I’d like to ask a question about the NeoCutis line. Originally NeoCusti was all about growth factors, much like their competitor–Skinmedica. However, they have added to their original line with their new MPC technology. According to them, growth factors are great for maintaining, but not for manufacturing collagen and elastin. The MPC are synthetic, or, “hand crafted” peptides that NeoCutis’ formulator spent years coming up with. So the products, the best one being MicroSerum, will firm the skin as well as help with fine lines, etc.
    Can you please tell me your thoughts on this line.

    Thank you,
    -ellen

    • drjohn says:

      Hi Ellen. Don’t know much about this company. But, the problem with new or custom peptides in the hands of cosmetic formulators is that they are a black box. They invent them in secret laboratories, subject them to ridiculous in vitro testing that proves nothing, then conduct an equally worthless non-controlled clinical trial showing that some people like it. Cosmetic formulators are rarely actual scientists (they seem to lack knowledge of basic physiology). There are literally hundreds of these peptides each touting the same claims, all from different supply houses. There is no independent validation of the mechanism of action, let alone how well it might work when embedded in the complex emulsions representative of skin care products. So – the answer is “who knows?”. maybe works, but excuse us for being skeptical. At least in the world of growth factors, there are hundreds of thousands of published papers where we know well the function of each of these “small proteins. The Neocutis PSP products are made from newborn foreskin fibroblasts. They don’t tell you that – they tend to keep it a secret, hide that fact, due to the obvious yecch factor. Its fun to go to a trade show and ask them about that – the sales people squirm, hem, and hah. So, why hide such things? Makes me not trust them. Fibroblasts make 1/10 to 1/50 of the concentration of growth factors that stem cells make in culture. Which is why they need to maintain large CM concentrations in the product in order to work at all, and also why fibroblast CM based products tend to smell a bit like wet gym socks. As you can glean here, we are skeptics when it comes to the world of cosmetic “science” as it is often practiced. More marketing than actual science.

  14. Cee says:

    You have written in a previous comment: ” It turns out that fat stem cells grown in culture behave a lot like fat cells in that they create such hormones. This may reflect the fact that it is hard to separate the fat stem cells from fat precursor cells – they don’t lose their “stemness” markers all that quickly as they begin to differentiate.”

    My question is, is it possible for a product using adipose stem cells to be cultured in a way that it didn’t have those inflammatory markers, or less of them, so that it was anti-inflammatory overall? If so, would such a product at least, then, be unproblematic for regular topical use?

    • drgeorge says:

      There are a number of ways to influence the secretome (what biosignals are produced) by stem cells in culture. Possible ways include altering oxygen and carbon dioxide concentration in which the cells are grown, or adding specific molecular stimulators or inhibitors. The specifics of how this impacts the fat stem cell secretome is therefore highly variable. The genetic heritage of the stem cell, however, is fixed and that has impact on secretome composition. Our contention is stem cells with an intrinsic genetic predilection to produce a predominantly antiinflammatory secretome, as bone marrow stem cells are prone to produce, makes them a preferred stem cell to culture in the production of topical skincare products. Our thesis has and remains these cells are primary agents of wound healing and tissue repair, which is not true of other stem cells. Reduction of inflammation in the skin is important in preventing damage and repairing injury. If there are fat stem cell-based topical products that are “unproblematic for regular topical use”, we would need data to change our opinion.

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