Plastic surgeon Randy B. Miller, MD, recalls when he and colleagues first realized the power of regenerative medicine within aesthetics. As a resident in plastic surgery at Baylor College of Medicine in the late 1990s, Dr. Miller said doctors were in the early phases of structural fat grafting.
“We didn’t know there were stem cells in adipose tissue, but we were seeing tremendous improvement in the texture and quality of the skin. I was actually even seeing it in reconstructive patients – when MD Anderson patients would come in with radiation fibrosis to the skin. Injecting fat in adipose tissue in those areas completely eliminated all the radiation damage,” according to Dr. Miller, who is a recognized expert in stem cell research and therapy.
The question of why surrounding skin improved post fat grafting remained until 2001, when mesenchymal stem cells (MSCs) were discovered in adipose tissue. That’s when it all made sense, Dr. Miller expressed.
“Since that time, stem cells have been used to regenerate heart tissue. They have been used to help patients with COVID-19 and pulmonary fibrosis be taken off ventilators,” Dr. Miller reported. “The proof of concept is already there. Stem cells eliminate scar tissue and actually stimulate the regeneration of new tissue.”
Fertile Ground for Regenerative Aesthetics
The American Society of Plastic Surgeons defines regenerative medicine as: “... the science of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal form and function. This broadly encompasses the use of cells, tissues, drugs, synthetic biomaterials and devices to help patients heal more effectively from trauma, cancer therapy, other disease processes and birth anomalies. Regenerative medicine therapies can have goals of both healing damaged tissues and forming new tissue.”
“We can do lots of beautiful things with the structure, volume and tension of the skin, etc.,” Dr. Miller began. “But to be able to stimulate the regeneration of new tissue and bring new tissue into the area, that is what I think is very exciting about the concept of regenerative aesthetics.”
Today’s popular regenerative aesthetics therapies include platelet-rich plasma (PRP), nanofat and microfat grafting, and exosomes.
PRP: Tried, True and Mainstream
Dr. Miller pointed out that PRP is tried and true in aesthetic medicine, but what many don’t know is that while PRP regenerates tissue with growth factors from platelets, it has little to no stem cells.
“I would say outside of the orthopedic world, PRP has been used most commonly for hair restoration. Using PRP as a filler has been a failing concept because it is not a filler. However, topical application or application after microneedling has been popular and... there is some good data to show that is a very helpful adjunct,” Dr. Miller noted.
Michael Somenek, MD, a facial plastic and reconstructive surgeon in Washington, D.C., added regenerative aesthetics and began conducting clinical trials for regenerative products about eight years ago.
“The uses for PRP have expanded over the years. When I first started using it, we were applying post-laser resurfacing and we still do that. We were putting it under facelift flaps and it expanded into the realm of hair – injecting it to help encourage new hair growth and improve the quality of hair,” Dr. Somenek shared.
One other PRP application is in personalized skincare, according to Dr. Somenek. “We draw the patient’s PRP and put it in serum vials of a stabilized solution to keep the platelets alive. The patient goes home with it and is able to apply their own growth factors to their skin on a daily basis,” Dr. Somenek expressed. “I will do laser resurfacing and set the patient up to get their blood drawn, making their skincare products in the office to help throughout the healing process.”
Harnessing the Power of Stem Cells from Fat
There are lots of stem cells in adipose tissue, but microfat transfer in general is reserved for filling in aesthetic medicine, according to Dr. Miller. Adipose transfer for filling leads to skin quality improvement, but microfat is too thick to use in the superficial skin.
“Nanofat is an FDA compliant process, where we are resizing the fat tissue...eliminating the adipose cells and preserving the mesenchymal stem cells,” Dr. Miller explained. “Those stem cells can be injected directly into the dermis, where you would never inject a filler. We have good data and great collaborators in Europe who we work with to develop nanofat to the point where we can inject it directly into the skin of the lower eyelids and completely erase hyperpigmentation with 15- and 20-year follow-ups showing maintained eradication of dark circles under their eyes. Amazing.”
The Great Promise of Exosomes
Exosomes can be derived from any source of stem cells. Stem cells communicate with tissue by stimulating the growth of new lung tissue, heart tissue, skin, or blood vessels, Dr. Miller advised. “But they don’t connect with the tissue directly, they send messengers. And the messengers have what is called messenger RNA, so basically it has signals within the exosomes.”
“In regenerative aesthetics, we use mostly adipose-derived stem cells. We find the highest concentration of the cells that we want, which are the mesenchymal stem cells, in adipose tissue,” Dr. Miller stated.
Globally, companies are manufacturing exosomes from adipose stem cells for the development of bio-drugs, but many who offer exosome therapy have little to no training or knowledge and are using exosomes illegally, Dr. Miller reported.
The average concentration is about 2.5 billion exosomes in 5 ccs of a regenerative exosome product. Instead of harvesting and growing a patient’s stem cells, companies are developing off-the-shelf products for aesthetic treatments. “It is illegal to inject those into the body,” Dr. Miller noted. “However, there are currently some formal drug studies using exosomes being done for the FDA, so it won’t be long before there are approved exosome-based drugs,” Dr. Miller projected.
Dr. Somenek thinks exosomes will be the next big area to go mainstream in aesthetic medicine. “I definitely still think there is a lack of regulation, specifically in terms of understanding the source, the concentration and the quality of the exosomes,” Dr. Somenek indicated. “But exosomes definitely have the power to do more than PRP. They literally are the most pure form of messengers that carry healing power and signal active regeneration into the tissues.”
Aesthetic practices are using topical exosomes with proven success after microneedling treatments.“We know that if we put exosomes on the skin after microneedling, it is really effective,” Dr. Miller shared. “But it is best to use microneedling with energy and non-insulated needles, then the tracks from the microneedling where the needle goes in and out don’t bleed, and there are temporary channels in the skin to allow for penetration of exosomes.”
Dr. Somenek is conducting research to study the use of one company’s topical exosomes and says that while the results are not yet public and he cannot share the company’s name, he has seen visible changes in skin quality from applying this topical to the skin with no other treatment.
Glynis Ablon, MD, associate clinical professor at UCLA and founder of the Ablon Skin Institute & Research Center in Manhattan Beach, Calif., agreed that exosomes are the next frontier in regenerative medicine. She uses EXOVEX from Exocel Bio (Scottsdale, Ariz.), which employs a proprietary incubation medium and a stringent process to produce high potency and safe exosomes.
EXOVEX, is designed as a companion product for skin and hair rejuvenation, used in post-microneedling or energy-based aesthetic applications. The non-lyophilized, live exosomes with growth factors and miRNA in EXOVEX help reduce the signs of aging, alleviating the stress of modern living and promoting healing for all skin and scalp types, according to the company.
“I love EXOVEX for skin rejuvenation and can’t wait until it is approved for the many other skin and hair changes,” Dr. Ablon stated. “I typically use it with microneedling and fractionated lasers, but just started applying it with dermo electroporation, or needleless applications. My patients quickly note after a few days how their skin is looking smoother, softer and even glowing.”
Lisa Espinoza, MD, of La Chele Medical Aesthetics in New Hope, Penn., uses EXOVEX in a variety of ways. “Once our patients try EXOVEX in conjunction with their treatment they never go back to device monotherapy as the results are quite remarkable,” she noted.
“We additionally use it for hair restoration as an alternative to PRP. The advantages tend to be more robust hair growth with less maintenance treatments required. Your PRP is as good as your age and health conditions, but EXOVEX is consistent and reliable,” she said.
Anil Rajani, MD, of Portland, Ore., incorporates AnteAGE MD (Irvine, Calif.), a growth factor-based, at-home hair regrowth product without added hormones or invasive procedures. The AnteAGE kit contains two tools to stimulate blood flow and encourage hair growth as well as a bottle of Hair Serum – which is formulated with specialized WNT1 Growth Factors to arouse dormant hair follicles and promote natural hair growth, filling in areas that are sparce, and improving the quality of existing hair, according to the company.
Dr. Rajani recommends that patients use it as a standalone treatment, as well as incorporate it into injectable treatments, such as platelet-rich fibrin with microneedling.
“Ideal candidates for treatment are those who have noticed declining hair either post COVID-19 or androgenic hair loss. Patients love the results and love to have an at-home option.,” he said.
“BENEV (Mission Viejo, Calif.) has the leading and most innovative regenerative trifecta in their portfolio,” Richard Jin, MD, PhD, from Mission Viejo, Calif., explained. “They have transformed my practice and thousands of other leading medical practices all over the globe with their exosome technology (Exosome Regenerative Complex and Exosome Regenerative Complex +), PDO technology (MIRACU PDO Threads), and RF Dual Wave Microneedling technology (Sylfirm X Ultimate Edition).
“Their portfolio is backed by clinical studies and driven by results,” Dr. Jin continued. “I appreciate that I can truly rely and trust them as my medical aesthetic partner to provide me with only products that are properly registered, cost effective and results driven.”
Youthology, Jason Rupeka, DO’s regenerative aesthetic medicine practices in Ohio, feature biostimulatory products, which he qualifies under the regenerative aesthetics’ umbrella.
One of those products is Bellafill® from Suneva (San Diego, Calif.), the only FDA-approved collagen-based dermal filler with polymethyl methacrylate (PMMA) microspheres. The collagen gel in Bellafill, which is approved for patients 21 years and older, provides immediate volume and lift to correct wrinkles and acne scars for up to five years. Once injected, these microspheres work to stimulate the patient’s own collagen, providing structural support for smoother-looking skin, according to the company.
“My approach is to help rejuvenate the skin, so Bellafill naturally lent itself to this philosophy,” Dr. Rupeka began. “It allows me to help my patients achieve a subtle immediate result due to the volume that the bovine collagen gel provides, while treating their skin/tissue over time through the neocollagenesis that the PMMA causes.”
Dr. Rupeka, who is the number one Bellafill user by volume worldwide, uses it in combination with Sculptra (injectable poly-L-lactic acid from Galderma), fat and PRP.
According to him, patients appreciate that they don’t have to replace the product as often as they would with a hyaluronic acid (HA) filler.
For clinicians, a keen knowledge of the anatomy, as well as where and how to inject Bellafill, is important, Dr. Rupeka advised, as it lasts longer than HA fillers and is not as easily corrected as HA fillers.
Challenges Remain for Even Credible Clinicians
While PRP is widely used and nanofat is FDA compliant, there remain quality issues including with instrumentation design and consistency of results.
For example, the way in which companies harvest exosomes lacks uniformity and is company specific, Dr. Miller reported. “So, you may get one company that is a bad exosome provider and one company that is a very pure exosome provider. The buyer must beware. The other buyer beware tip is with PRP systems. There are a lot of PRP systems out there that don’t necessarily concentrate blood very well even though they are very well marketed.”
A lack of regulation is a common theme with regenerative aesthetic treatments, according to Dr. Somenek. “There are many companies that sell PRP tubes for drawing blood in the office and spinning it down, but we don’t exactly know the quality and quantity of the PRP,” he said. “It is also very patient dependent.”
In 2020, the FDA released a consumer alert on regenerative medicine including stem cells and exosomes noting that the agency is concerned with how regenerative medicine products are being illegally used and falsely marketed.1
Stem cell and exosome products are regulated by the FDA, and currently, the only stem cell products that are FDA-approved for use in the U.S. are derived from umbilical cord blood and approved for use in patients with disorders that affect the production of blood. There are currently no FDA-approved exosome products, according to the FDA.
Drs. Miller and Somenek recommend the aesthetic doctors who want to begin offering regenerative aesthetic therapies learn all they can by attending panels at credible aesthetic meetings and doing their research. “If you are looking to get into some form of regenerative medicine, PRP is a great avenue into this world. It is fairly straightforward; the products are easily accessible; and there is a wide variety of things that you can use it for in your practice,” Dr. Somenek concluded.
1. Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. fda.gov. (2020, July 22). Retrieved March 23, 2022, from https://www.fda.gov/ vaccines-blood-biologics/consumers-biologics/consumer- alert-regenerative-medicine-products-including-stem-cells- and-exosomes#:~:text=The%20US%20Food%20and%20 Drug%20Administration%20%28FDA%29%20has,the%20 conditions%20they%20can%20be%20used%20to%20treat.