Mark Twain, an American author and humourist, once said life would be infinitely happier if we could only be born at the age of 80 and gradually approach 18. Human quest for youth and overcoming death begins from ancient time. In the medieval age, the Fountain of Youth was popular myth and illustrated in the year 1546 in a painting of Lucas Cranach, which depicted a spring that supposedly restore youth of anyone who drink it or bathe in its water. Alexander the great, who conquered most of the world before he died around 323 BC was said to have searched for Fountain of Youth in the dark valley. In fact, as society whole today has not lost its fascination with immortality or prolonging the aging process. Only difference is that rational of Fountain of Youth is supported by modern scientific knowledge and tools to interfere with aging process or regenerating tissues in age related diseases.  

Aging is a progressive loss of physiological integrity impaired function and increase vulnerability to death. One of the first signs of aging is skin wrinkles, skin pigmentation and hair loss. Aging research has seen unprecedented advances in the last few decades, particularly with the discovery that rate of aging is controlled by genetic pathway and biochemical process that conserved during evolution.

Several therapeutic candidates for anti-aging or age related diseases are under research including stem cell therapy. Current global anti-aging market is growing at a CAGR of 7.8 per cent between 2013 and 2019. Current market value is US$ 122.3 billion and it is expected to reach US$ 197.7 billion by 2019 end.  Market survey report stated that more than 8,000 individuals are added per day to count of people above 65 and it is expected to continue for the next 18 years. Global anti-aging market is further boosted by generation Y and post pregnant people. Moreover, availability of surplus funds continues to drive the market. Majority of the anti-aging products globally can be purchased without any doctor’s prescription including stem cell based products that helped to create a marketing opportunities for industry due to unclear regulation, most notably the development of a direct to consumer market for unproven anti-aging therapies without knowing its long-term consequences.

Stem cell has huge potential
Stem cells are building block for all the organisms. They can divide and renew themselves throughout their life, differentiating into specialized tissues needed during development and as well as necessary to repair tissues. Stem cells have demonstrated their potential to develop into practically all types of specialized cells and tissues of the body and hence opened up a new era of regenerative medicine and promising the replacement or regeneration of damaged cells and tissues or organs and become a symbol of hope for countless human ailments.

But, stem cell therapy has been flaunted liberally in many countries including India and unproven therapies are blatantly on sale and creating total disconnect between what is offered, actual reality, the public expectations and proven validated medical knowledge. This phenomenon of stem cell hype has helped to create a marketing opportunities for industry, most notably the development of a direct to consumer market for unproven stem cell therapies for almost every known ailment and conditions. Stem cell based anti-aging cream, serum and lotions are the new entrant in this area with no conclusive clinical and scientific evidences. Following points showed that why stem cell and its extract just cannot work in the anti-aging cream?

Plant stem cells
Market is flooded with plant stem cell anti-aging cream. The stem cells found in anti-aging cream are obtained primarily from plant and fruits like Swiss apples, edelweiss, roses, date palm, narcissus bulb, bogbean and gotu kola. Extract of these stem cells are normally added in the cream or lotion. Almost all the companies are making tall claims that these plant or fruit extract encourage the growth of your own stem cells and possibly trigger anti-aging effects. It is scientifically impossible. The bio-chemical massagers in the plant cells do not communicate with human stem cells in the skin or elsewhere unless human start synthesizing chlorophyll in their body. Growth factors have species specific effect and cannot work on other species.
   
Human stem cells
Several brands of anti-aging creams are claiming to have fat derived stem cells in it. Human stem cells are the living tissue or cells. They cannot survive outside of the incubator and without nutrient media. It is therefore unlikely that the cells would be effective by the time they grow in the laboratory and reach to your skin. They simply cannot survive in chemically enriched cream and that to at uncontrolled environment. Size of stem cell is big enough (10-12 µm) and simply cannot penetrate into the skin. Major function of skin is to act as anatomical barrier and protect it from all the pathogen and external material. Several companies argue that stem cell secretes growth factors and cytokines and that penetrate into the skin to give desirable results. It is difficult to understand how dead stem cells secrete growth factors and cytokines?  

Human stem cell conditioned media
Several companies have now started using other stem cell alternatives including stem cell conditioned media. Many claim as potent stem cell bio-factors. It is believed that stem cell conditioned media contain important growth factors and cytokines that may help in regeneration. But, all the growth factors and cytokines present in the conditioned media are below detectable limits. Our group has analysed stem cell conditioned media in high throughput multiplex system and we observed that conditioned media has several growth factors, cytokines, chemokines, basic proteins and adhesive proteins at below detectable limits and has no clinical relevance. They can only be detected and measured if conditioned media is concentrated by minimum 20 folds. We have also analysed stem cell conditioned media by liquid chromatography-mass spectroscopy (LC-MS) and observed just 78 proteins compared to 479 unique proteins present in human plasma. Therefore, following points will explain why stem cell conditioned media has no clinical relevance in anti-aging cream?

Growth factors and cytokines are signalling molecules between the cells and that has to bind to specific receptors on the cell surface of their target. Intact skin does not have any exposed receptors through which the growth factors can bind in order to promote any action. Remember, the intact skin is designed to keep things out especially large things like pathogen, viruses, cells and any large protein. It is a protective covering of our body. Growth factors and cytokines are large size proteins and just cannot penetrate in the skin epidermis to take action. For example, many of you must have seen spitting cobra spitting venom on the body and face. But, skin protects it from such highly potent venom entering in the body. Snake venom is a protein and difficult to enter through skin. Therefore, such claims are absolutely unscientific and misleading.

It is a known fact that growth factors and cytokines are unstable at room temperature. Data demonstrated that almost all the growth factors and cytokines gets denatured at room temperature within 48 hours. They can only be stable for one week if preserved under refrigeration of 4 to 8oC or stable for 3-6 months if tag with carrier proteins and preserved under minus 20oC. Companies do not recommend storing their products at minus 20oC or under refrigeration. How can these growth factors and cytokines remain stable in anti-aging cream for so long at room temperature is a big question?    

Level of growth factors and cytokines secreted by the stem cells in media is below detectable limits and hence may not have any clinical relevance unless; the conditioned media is concentrated minimum 20 times. Using concentrated conditioned media is unaffordable for the companies and customers since it escalates the overall cost by many folds.

Several companies have given supporting data on in vitro fibroblast assay. Sure, these growth factors and cytokines will show higher proliferation rate and increased collagen synthesis. Growth factors and cytokines will act on these cells since they are individual cells with presence of target receptors on their surface. But, these assays cannot be extrapolated for intact skin. Hence, logic of using fibroblast assay for anti-aging cream is false and misleading.

Companies intentionally avoid mentioning the amount of each growth factors present in the anti-aging cream in the formulation. Nobody knows actual dose that gives optimal results. Even if we consider that anti-aging cream has active growth factors and cytokines and they penetrate into the skin, there is a serious risk of cancer development if use as per recommendation. One such growth factor product available in the market is Becaplermin that contains platelet derived growth factor (PDGF) and normally used for diabetic foot ulcer. Results showed an increased rate of mortality secondary to malignancy if used more than 3 months. Therefore, it is recommended that Becaplermin should only be used when the benefits can be expected to outweigh the risk. The US Food and Drug Administration has categorized this product under black box. Therefore, users should beware of such stem cell based anti-aging products.        

Risk factors
This stem cell based anti-aging cream need to be applied twice a day for 4-6 months continuously to get optimum results. One must remember that stem cell beauty products are often formulated with other effective phytochemicals, anti-oxidants, moisturizer, etc. which may be actually responsible for benefits. It only works because of moisturizing capability present in the anti-aging cream. Data proved that even application of Vaseline for 3-6 months gives similar results. Most of the clinical trials are poorly designed, without any controls (normally split face study is recommended) that do not provide strong clinical evidence (safety and efficacy) and are largely unproven by any scientific standard. Using anti-aging cream for so long is potentially dangerous. Several anti-aging formulations are now linked with breast cancer.

Lollipop marketing
If one browses the internet for stem cell based anti-aging products, you will find hundreds of them with tall unproven claims. Most of the marketing promotion of stem cell based anti-aging products has been largely based on anecdotal evidences and extrapolation of imaginary mechanism which is ranging from un-reasonable to ridiculous and most citing unsubstantiated claims. Unfortunately, in India, several dermatologists, plastic surgeons, and physicians are prescribing such products merely to provide some novel things to customers due to extreme professional competition and also for their short-term financial gain. Almost all the stem cell companies in India are currently offering stem cell anti-aging therapies to the customers without knowing any scientific and clinical evidences and without knowing its future consequences. It is nothing but a junk science.           

Industry has given a new twist to this anti-aging business and coined a word ‘Cosmeceutical’ giving an impression to customer that, cosmetics has drug like benefit. The FDA does not recognise term cosmeceutical and thus not subject to its regulatory scope. This is a marketing gimmick and giving you an impression that you are getting one of the most advanced treatment and that is a biggest bang on your pocket.

Recent report of Rachul et al., in International journal “Aesthetic Surgery Journal” studied all the stem cell anti-aging products and the company’s website about their claims. They have demonstrated that none of the claims have scientific evidences, their mechanism of action and risk. Authors have highlighted the need to educate patients and public on the current limits of stem cell application and possible risk in this context.    

It is therefore important to provide unbiased and substantiated information to the customer that will allow patients to base their decisions in science, not marketing hype. Otherwise the void will be filled with promotional misinformation and financially driven pseudoscience and could be a ‘scienceploitation’ of customer. This unfortunately is already happening and I believe will continue to get worse and more confusing for unsuspecting patients unless we make a concerted effort to combat it with validated, scientific, and understandable information. Unfortunately, all the regulatory bodies like Drugs Controller of India (DCGI), Indian Council of Medical Research (ICMR) and National Apex Council for stem cells Research (NAC-SCR) are turning blind eye to this ongoing exploitation and putting the customer at great risk. Stem cells have huge potential but incomplete, wrong and biased information to the customer will damage the stem cell industry beyond repair.


(Author is founder and managing director, Aureostem Research Pvt Ltd, Mumbai)