Arguably, the most important development in the field is the overall shift in mainstream industry and consumer thinking toward the holistic, the natural and wellness. A tipping point has been reached, and it is high time, according to dermatologist and dermatologic surgeon Shino Bay Aguilera, DO, director of Shino Bay Cosmetic Dermatology (Fort Lauderdale, Fla.). “I feel like we are at the pinnacle, hurtling toward regenerative solutions and overall wellness, because patients and practitioners alike are finally beginning to look for more natural solutions to get more natural-looking results. As we better understand the role of genes and tissue health at the cellular level, we are changing the way we treat aging.”
Traditional practices are adopting holistic philosophies, and new integrated wellness-based practices are becoming ubiquitous. Among those with longstanding experience in the art and science of functional, regenerative and aesthetic medicine, is aesthetic and anti-aging medicine expert Jennifer Pearlman, MD, director of PearlMD (Toronto, Ont., Canada). “Regenerative aesthetics transcends our desire to optimize and refresh as an emerging approach to reprogram youth and reset our aging. The new science of longevity reveals that aging is reversible and through the use of regenerative factors such as exosomes, growth factors and stem cells we can reprogram aging tissues such as skin and hair to be young again. But as we are all unique, the approach must be highly individualized and holistic. ’One-and-done’ just does not cut it anymore, and as we dig deeper into these emerging tools while learning more about old ones, an inside-out approach to health should be the new norm. As we move forward it is becoming starkly clear, we need multi-modality wholistic bespoke approaches that evolve over time for our patients.” 
Rahi Sarbaziha, MD, director of Dr. Rahi’s Integrative Aesthetics (Beverly Hills, Calif.), epitomizes this multi-modal approach. “My practice offers a wide range of services with a lifestyle/ wellness approach to care,” she explained. “Regenerative aesthetic products are a large and growing part of this. I combine as many therapies as possible, including regenerative and more traditional modalities such as injectables. Exosomes and PDO threads, for example, work together incredibly well.”
Another question: How do we do this safely and responsibly, fighting the urge to succumb to the excitement and fall into the hype trap? Few areas generate more controversy than stem cell research. In fact, a recent article2 in Regenerative Medicine highlights the complicated issue in more detail, breaking down responsibility as accountability, liability, obligation and virtue, framing these concepts as a strategy for approaching stem cell research as a whole.
It is complicated, according to Gordon Sasaki, MD, clinical professor in the Department of Plastic Surgery at the Loma Linda Medical University Center (Loma Linda, Calif.). “Key disadvantages are inherent when examining cell-based therapies such as restriction to autologous usage; differences in cell survivability, apoptosis and senescence; presence of heterogenous (mixed) cell populations; need for complicated procurement, processing and expansion procedures; and concerns for contamination and stability,” he noted.
“Cell-free based therapies have certain advantages in that they may be used for allogeneic and autogenous applications, exhibit less immunogenicity, possess product stability and are readily available for usage as an off-the-shelf product,” Dr. Sasaki elaborated. “The U.S. FDA has clearly stated that all mesenchymal stem cell by-products, if derived from more-than-minimally manipulated processes for regenerative therapies, are to be regulated as a Human Cells, Tissue, and Cellular and Tissue-Based Products (HCT/P) drug. The entire industry is trying to refine just what that means and how to best proceed with the primary goal of patient safety. Physicians must embrace the sobering reminder that ‘regulatory compliance’ does not mean ‘approval’ for an ‘intended clinical use.’ Currently, the use of cells or biologic by-products are considered experimental and remain under strict regulatory oversight.”
According to plastic surgeon Gregory Buford, MD, medical director of Beauty by Buford (Lone Tree, Colo.), autologous stem cell banking has great potential. He has been working with ACORN (Toronto, Canada), a company in early stages of developing this technology as well as a subscription business model allowing access to one’s stem cells. “One of our medical team plucks 40 to 50 hairs from the back of your head using a vibrating device to make the procedure as comfortable as possible,” he explained. “Your stem cells 
are derived by processing these hair follicles. After banking your stem cells, they can formulate a more vibrant platelet-rich plasma (PRP) like product with theoretically less variation than PRP, and if harvested at a younger age it would be stronger
Philippe Magistretti, MD, co-founder of Summit Clinic (Crans-Montana, Switzerland), is lead author in a study of Exokine, a youth-boosting autologous treatment. With this treatment whole blood is incubated at 37° C for eight hours in order to release key growth factors from platelets and into the serum, for later injection. “The challenge with this developing method is that it is inconvenient,” he explained. “Like PRP it uses the patient’s blood but once drawn, processing takes time so the patient must return later. Therefore, avenues of development include preserving and storing the components such as freezing, which has been proposed by the manufacturer, but it becomes a regulatory nightmare because we are storing blood components.”
Most prominent in the stem cell realm are exosomes – the messengers that carry the powerful compounds that activate and upregulate regenerative processes at the cellular level.
Jordan Plews, PhD, co-founder and chief executive officer (CEO) of ELEVAI Labs, Inc. (Newport Beach, Calif.), has been working in the field since the beginning of his academic career and has been entrenched in the industry throughout. “Exosome therapy does what PRP or stem cell therapies do, except better, because they are the actual components of the PRP or stem cells which stimulate the very processes we are trying to harness,” he said. Currently, exosomes are FDA approved for topical use only.
The ELEVAI E-Series™ products were developed as a post-treatment aftercare system. Both empower and enfinity products contain exosomes – ultra-small, nanoparticle compartments packed with growth factors known to support skin health. Patent-pending ELEVAI Exosomes™ are the powerhouse ingredient in these products, mimicking the elegant repair processes of nature and paired with a selection of high-quality science-backed ingredients to provide regenerative skin health for any skin type.
Together, empower and enfinity provide optimal post-treatment and daily care to ensure complementary regenerative effects. “We have found great utility for the post-procedure product, empower, in my office,” said Natalie Curcio, MD, of Curcio Dermatology in Nashville, Tenn. “We use it for a variety of laser and energy-based devices including particle-free microdermabrasion, microneedling, radiofrequency (RF) microneedling, vascular lasers and non-ablative fractional resurfacing. And once they have experienced empower, patients are eager to try enfinity.”
By utilizing anti-inflammatory growth factors and cytokines, AnteAGE MD (Irvine, Calif.), announced their newest topical Exosome Treatment Solution. For more than 10 years AnteAGE MD has been formulating solutions for pre-treatment, in-office treatments and post care. Quickly restoring skin health at the cellular level allows for a speedy recovery, decreased downtime and optimal patient outcomes. “The science backing AnteAGE is significant,” reported Jason Emer, MD, director of Emerage Cosmetics (Beverly Hills, Calif.). “There is no other company that has this level of science with regards to stem cells, specifically with growth factors that decrease inflammation, rebuild the skin, stop the aging process from occurring, and help build collagen. It has everything your skin needs to restore itself and to decrease inflammation.” AnteAGE offers a complete portfolio of skincare, brightening, hair restoration and vaginal care products.
Extracted from the mesenchymal stem cells of ethically-sourced human umbilical cords, MG-EXO-SKIN™ from Dp Derm (North Miami, Fla.) is a regenerative, biomimetic and multi-potent topical complementing in-clinic regenerative procedures like microneedling and mesotherapy, or heat-based procedures such as lasers or RF microneedling. It is never frozen and requires no refrigeration or reconstitution; delivering truly unprecedented results minus the complications associated with autologous procedures. And, no additional time is spent on processing and preparation.
In addition, the Company’s DP4 Microneedling pen is an advanced fractional micro-channeling device that creates micro-injuries which trigger a natural process of increasing the production of collagen and elastin. FDA cleared for treating facial acne scars, this device offers a dedicated Scar Treatment (ST) setting. “This is the first medical-grade device of its type,” Dr. Aguilera noted, “and can be calibrated to provide a controlled injury to the skin to give us the desired effect. It is especially useful to us in South Fla. where we must be very careful treating darker skin types.”
The Regenerative Trifecta from BENEV (Mission Viejo, Calif.) includes SYLFIRM X® an FDA-registered pulse wave and continuous wave RF device for non-invasive skin revitalization; the BENEV Exosome line of cutting-edge scientific biotech topicals to rejuvenate and regenerate the skin and scalp; and the MIRACU® line of PDO threads, each featuring unique innovations that make them distinct from each other and the 
competition. “BENEV is continually developing regenerative solutions that target cell regrowth, lasting collagen regeneration and harness natural processes,” explained Suneel Chilukuri, MD, director of Refresh Dermatology (Houston, Texas). “The Company’s products are a staple in my practice. I trust the science that’s been conducted to support the proper use of the products and I have seen firsthand just how powerful they can be. I rely on the consistent quality of the products.”
Although not specifically exosome products, many emerging therapies similarly seek to harness growth factors, peptides and more to work their science-based magic at the cellular
level. Topical SMART eXo from Smart Solutions RX (Glen Mills, Pa.) is a biological nanoparticle therapeutic solution with multiple applications including use in a holding solution for bathing grafts prior to implantation during hair replacement surgery. Contained in the 8 mL solution are more than 100 billion extracellular vesicles, quantified and qualified with lab-identified micro ribonucleic acid (miRNA) specific to communication in the hair follicle pathway, which is important to follicle regeneration and healthy hair growth. It is manufactured with the highest safety standards using a patented sterile extraction process with no dilatants, and is non-expanded/non-cultured, non-nucleated and acellular (not classified as an HCT/P).
“Hair surgeons are using nanoparticle therapies like Smart eXo that contain hundreds of proteins, hyaluronic acid and cellular messengers to reduce inflammation and reinforce rapid and healthy growth of transplanted follicles,” stated Barry DiBernardo, MD, founder of New Jersey Plastic Surgery in Montclair, N.J. “While further studies are necessary, in my opinion, this topical addition to hair regeneration therapies is extremely promising.”
DMK StemZyme treatment from Danné Montague-King Co. (DMK) in Santa Fe Springs, Calif., is a smart non-invasive, non-immunogenic approach effective in basal level skin metamorphosis. It activates one’s own stem cells, differentiating them to form new epidermal skin organelles without creating immunogenic and inflammatory shock, to manage aging-related skin impairment,” explained Jayant Lokhande, MD, chief scientific officer at DMK. The eight-product regimen, designed to be used in conjunction with select DMK products, includes Pore Dilating Serum, Keratin Conformation, Skin Nutrient Paste, Mitosis Stabilization, Skin Defining Emulsion, Age Management Lotion, Skin Refining Lotion and dietary supplement Integumentary System Support. “When one needs to address epidermal cell damage due to biological aging and related predisposing factors, personal adult epidermal stem cell activation is an innovative and effective approach to revive the epidermis,” he added. 
Manufactured in the U.S., and formulated for physicians specifically, LC Cell from Love Beauty Pro & Medical (Woburn, Mass.) features advanced active ingredient technologies and innovative botanically sourced ingredients. The blend of science and nature provides a continuum of optimal results from the treatment room to the home care regimen via specialized products that yield visible results for every skin type and indication, and complement professional aesthetic procedures. Oculofacial plastic surgeon Paul Brannan, MD, owner of Aesthetic Eye and Surgical Arts (Sarasota, Fla.) has been using the LC product line for the entire time his practice has been open. “We carry the entire line of the products and get great patient feedback,” he began. “My favorite is definitely Ageless Eye Serum, recommended to my cosmetic patients for enhancing the appearance of their eyelids. As an adjunct to procedures such as upper or lower blepharoplasty it really augments procedures, reducing healing time and minimizing wrinkles and scarring. I cannot say enough good things about LC Cell.”
Rion Aesthetics (Rochester, Minn.) offers ( plated )™ Skin Science containing Renewosome™ technology, a proprietary ingredient that harnesses the power of platelets to help provide a defense against the visible signs of aging, the appearance of wrinkles, redness, brown spots and dullness. Currently, ( plated ) comes in three different formulations: INTENSE, DAILY and CALM. INTENSE serum is a highly concentrated formula enriched with growth factors and antioxidants, ideal for those with more damaged skin. The DAILY serum is a luxurious formula that is perfect for daily hydration and overall maintenance. CALM is designed for use following aesthetic procedures, providing cooling hydration and reducing the appearance of redness post-laser. These products represent a new approach to skincare. 
The most momentous issue on the regenerative aesthetics horizon, according to Dr. Pearlman, is the rapid acceleration of scientific progress. Human immortality is within reach, she noted. “By future proofing our health, vitality and beauty we can maximally benefit from the emerging science on the horizon. While the regulatory environment continues to evolve and new tools, technologies and indications become available, we will have more options than ever to age well from the inside out.”
References:
1. Zarbafian M, Fabi S, Dayan S, Goldie K. The emerging field of regenerative aesthetics – where we are now. Dermatol Surg 2022;48(1):101-108.
2. Assen L, Jongsma K, Isasi R, et al. Responsible innovation in stem cell research: using responsibility as a strategy. Regen Med 2023 18:3, 275-284.
3. Magistretti P, Bertossi D, Pirayesh A, et al. Exokine and the youth-boosting treatment based on one’s own serum: wheat and chaff. Facial Plast Surg 2022;38:177–181.
