What is normalcy? This summer, physicians and practices were finding a semblance of familiarity back in day-to-day operations, with the rise in people vaccinated making it possible for many states to remove masking mandates and lift some of the heavier COVID-19 restrictions.

Then along came the Delta and Lambda variants.

Many are left asking difficult questions regarding vaccination status, booster shots, and what the future of the pandemic holds. For now, normalcy looks like wearing masks to keep immunocompromised people safe, urging the unvaccinated to get vaccinated, and continuing to input exhaustive safety and cleaning measures in the practice.

In this Fall issue, Jack Zamora, MD, highlights stem cell use for COVID-19 patients and its overarching potential in wound healing, Alan J. Bauman, MD, ABHRS, FISHRS, and Jessica A. Shepherd, MD, MBA, FACOG, discuss why physicians shouldn’t shrug off postpartum hair loss, a study examines rare cryolipolysis complications, and aesthetic physicians highlight the power of dermatology TikTok.

Click on the cover below to read the digital issue and let us know what you think on our social media.

Articles

In this Fall issue, Jack Zamora, MD, highlights stem cells for wound healing, Alan J. Bauman, MD, ABHRS, FISHRS, and Jessica A. Shepherd, MD, MBA, FACOG, discuss why physicians shouldn’t shrug off postpartum hair loss, and aesthetic physicians highlight the power of dermatology TikTok. 

Innovative Perspectives: Aesthetic Authority Vol. 2: No. 3

What a difference just a couple of months can make. Things were rolling along and our practices and lives seemed to be getting back to some sense of normality. The pandemic had run its course. The pandemic seemed to be slowing…then along came the Delta and Lambda variants.

Now we are left to wonder whose statistics to believe. How many individuals have really been vaccinated? It seems as though I am seeing more unvaccinated patients than those who have received one of the vaccines.

More importantly, which vaccine is the most reliable and for how long does it really provide solid protection? I am hearing from vaccinated friends who were sick within the past month.

In recent days, it seems that many of my colleagues have already received their booster injections. All the while, the CDC is now making available, or even recommending, a booster no later than 8 months after the second injection. You have to wonder whether the immunity provided by the COVID-19 vaccine is not more in line with that provided by the influenza vaccine, because 6 to 8 months seems about right.

Personally, if this is what we must do to put this dark chapter in history behind us, then I am all in. This highlights the need to ask specific questions about our future in the pandemic, including the following:

Should we be forced to receive the vaccine if we wish to dine out, fly, attend a concert, go to a ball game, or even attend a live medical conference?

Moreover, should we require all our employees to be vaccinated to safeguard our patients, fellow employees, and prevent the practice from closure should an infection spread among key employees?

Should our patients and staff be required to mask up when entering our practices?

Should our children be required to mask up to attend their schools, or should schools be open at all?

Should we require polymerase chain reaction (PCR) testing for all our surgical patients? What about our injectable patients? Should they be tested?

At least 1 of our colleagues sadly passed away after acquiring COVID-19, conceivably from a lip injection patient. In Kentucky, the COVID-19 infection rate in mid-August exceeded all previous highs and the positivity rate was over 12%—also a record. What to do?

I know what we are doing in our practice, and that is protecting our patients and our staff as best we can. However, we are moving forward with our lives. The practice continues to encourage the unvaccinated among us to get vaccinated, but we do not believe it should be forced on anyone.

We continue to test all surgical patients within 36 hours of a procedure with a PCR test and confirm the morning of surgery with a rapid test. We test all patients who are receiving injectable filler treatments with a rapid test while they are awaiting the treatment. Additionally, masks are required for everyone entering the office.

I am very much looking forward to creating a safe environment in Miami’s South Beach at the Global Aesthetics Conference in early November. It is important to continue living our lives. Sharing time with trusted and likely vaccinated (many with boosters on board) colleagues is always much needed in this chaotic world.

In his latest editorial, Randolph Waldman, MD, discusses the Delta and Lambda variants of COVID-19, complex questions about vaccinations, and what boosters mean for the pandemic’s future.

There’s Nothing New About This “New Normal”

Botulinum toxin A (BTA) is effective in upper lip enhancement and in shortening the philtrum, according to study findings published in the 

Fillers are a common treatment to improve lip fullness. To see how BTA stands up in enhancing lip fullness, investigators examined 3 patients (2 women and 1 man) who had not previously received BTA. The mean age of patients was 28.7 years, and they were each given 4 U of BTA injections, 1 unit per site, in the upper lip at the vermillion border.1 Patients had 3-dimensional photographs taken prior to and 2 weeks after treatment to evaluate for lip fullness. Investigators measured the upper lip surface and 8 linear distances. These measurements were compared before and after BTA treatment.

Following the treatments, measurements showed taller upper lip vermillion height (

=.038) and shorter cutaneous upper lip height (

=.024).1Investigators noted that although it seemed upper lip surface area was larger, it was not statistically significant. All 3 patients experienced slight perioral muscular palsy and incompetence of the mouth that lasted 3 months, but they improved gradually after 1 month.

Because BTA interferes with lip function, the procedure should be avoided in patients such as singers who require high mouth competency, the investigators wrote. They also noted that patients should be informed beforehand that the procedure reduces the height of the cupid’s bow, resulting in a slightly flattened lip.

Joel Cohen, MD, FAAD, FACMS, ASDS, director of AboutSkin Dermatology and DermSurgery in Greenwood Village and Lone Tree, Colorado; fellowship codirector for the American Society of Dermatologic Surgery’sDermatologic Surgery Colorado Fellowship; and associate clinical professor at the University of California, Irvine, shared some clinical insights with 

He says he uses BTA for a prominent orbicularis oris muscle that has no imprinted lines.

“These are often younger patients,” Cohen explains. “[I see] the patients I address with botulinum toxin about every 3 or 4 months. I use very low doses, 10 to 14 units of Dysport [abobotulinumtoxinA] or 4 to 6 units of Botox [onabotulinumtoxinA], Xeomin [incobotulinumtoxinA], or Jeuveau [prabotulinumtoxinA].”

For some imprinted lines, Cohen says uses a 30- to 31-gauge needle for filler. “I go right into the edge line with filler,” he says. “And I often repeat this about every 6 months. This seems to stimulate some collagen, so over time people do this less frequently.”

Cohen also says that for patients with many imprinted, severely etched lines too numerous for filler or too small for filler, he prefers ablative resurfacing. “If they want to see major improvement with usually just 1 treatment, then I will do full-field erbium such as Sciton JouleX 2940, which takes 10 to 14 days for skin to re-epithelialize, but then [patients] often experience red to pink [skin] for 6 to 8 weeks.”

If patients want less downtime, he will do fractional ablative carbon dioxide or erbium laser, with time to re-epithelialize at approximately 5 to 6 days, and then the skin will be pink for a few weeks.

Cohen adds that “it’s important to point out that these treatments are not mutually exclusive. To prevent a lot of muscle contraction that could recapitulate edge lines, I do botulinum toxin very frequently a week or 2 before this type of resurfacing around the mouth.”

In many cases, he still uses fillers for volume support in the marionette area, nasolabial folds or cheeks, and sometimes in imprinted lines like the horizontal line of the depressor septi area.

“And then starting 3 or 4 months after the resurfacing, I will still use botulinum toxin to help try to prevent the muscle from contracting and reestablishing,” he says.

Li Y, Chong Y, Yu N, Dong R, Long X. The use of botulinum toxin A in upper lip augmentation

. 2021;20(1):71-74. doi:10.1111/jocd.13731

A recent study finds BTA an effective alternative to fillers, but it should be used with caution.

Botulinum Toxin A Effective in Upper Lip Enhancement 

Dermatologists and aesthetic physicians are using the social media platform TikTok to educate and market their practices. And it’s working.

“…TikTok holds great potential as a platform for disseminating educational information,” wrote authors of a 2021 article published in the 

Journal of the American Academy of Dermatology

And TikTok’s influence is only growing. For example, views for #acne on TikTok more than doubled from 3 billion to 6.7 billion from September 2020 to February 2021, according to the article.

Brooklyn, New York, dermatologist Angelo Landriscina, MD, started using TikTok regularly when the pandemic began. The platform in turn helped him build his dermatology practice, which he started in December 2020. Using the handle @Dermangelo and with more than 258,000 TikTok followers, Landriscina tackles topics such as skincare. He also busts social media-inspired “hacks” such as why people should not apply vodka to their faces.

“At the time, I was already active on social media, mostly on Instagram,” Landriscina says. “While my primary goal is to produce educational content for the public, many patients have found me via TikTok. Having a presence on social media has been very helpful in building my patient base.”

New York City-based celebrity cosmetic dermatologist Paul Jarrod Frank, MD, uses the handle @drpauljarrodfrank on TikTok. He capitalizes on social media platforms to drive traffic to his PFRANKMD aesthetic health care brand.

“At the end of the day, everything we do on social media is educational and leads back to the [return on investment] of bringing in new patients and building brand awareness,” Frank says. “TikTok is a platform where content needs to be quick and digestible, and it allows us to take our creativity to the next level, while still providing educational content.”

Frank discovered TikTok’s power when he contracted COVID-19.

“It was a very scary time, and I wanted to openly share my experience to educate others who may have been going through the same thing,” Frank says. “As one of the first people to document my COVID-19 journey, my videos began to go viral and started important conversations. My educational COVID-19 videos got over 4000 comments and reached over 3 million people all over the world. Our treatment videos also go viral as they show eye-catching procedures and results that followers may have never seen before.”

Despite being banned in some countries, TikTok is the seventh most-used social network with 689 million active users worldwide as of January 2021. The majority of TikTok users in the US are younger than 30, according to Hootsuite.com.

“Social media platforms such as TikTok are changing the way we connect and interact,” Szeto et al wrote in an article published in April 2021 in the 

TikTok offers a constant, addictive stream of short, catchy videos curated for users, with the potential for cross-generational appeal. It is user-friendly and shows viewers videos based on their interests, according to an email to

™ from 2 of the article’s authors, Colby Presley, DO, a practitioner in the Department of Dermatology at Lehigh Valley Health Network in Allentown, Pennsylvania; and Mindy Szeto, MS, Department of Dermatology at the University of Colorado in Aurora.

“Typically, TikTok users post and seek out content they enjoy, things they’re passionate about,” they wrote. “They can also ‘duet’ to build on existing videos and communicate with people around the world in real time, so it becomes easy to make and develop those human connections. Our published study also highlighted how TikTok videos are unique because they can be posted to Instagram as Reels. With this capability, TikTok can make its videos available on both their application and Instagram, presently the largest social media application by follower numbers. [Although] TikTok is currently used heavily in the younger generation, Instagram has a wider age range of users and those Instagram users can see TikTok videos.”

Providers can leverage the fact that consumers and patients are using TikTok to discover and discuss medical information to directly connect with the public, as well as promote their brand and practice, Presley and Szeto wrote.

“Interactive ‘duets’ are very popular on highly viewed skin care videos, and we encourage providers to use this feature to be a presence and provide guidance on what medical advice videos say and do,” the authors wrote. “However, it’s also very important, and we recommend, that providers conduct themselves ethically, being aware of privacy and confidentiality, explicitly disclosing conflicts of interest, and maintaining professional boundaries, among other social media best practices. Furthermore, the amount of inaccurate or misleading health care information being shared on these platforms is high. We hope that greater provider presence on social media can help dispel some of the health care myths.”

TikTok, as with most social media sites, does not verify users’ credentials. So anyone can say they are a medical professional and provide medical advice, according to Presley and Szeto.

Frank says TikTok gives him the opportunity to set the record straight on important safety measures such as the use of at-home hyaluronic lip fillers.

Some dermatology and aesthetic topics or themes really seem to strike a chord with TikTok users.

“Recent topics that have done well on my page include using benzoyl peroxide for acne, tips for saving money on prescription drugs, and the lack of data behind using rice water for hair growth,” Landriscina says.

To make TikTok work for their practices, clinicians need to spend time on the app. “[TikTok] is not the same as other social media platforms, so you should familiarize yourself with the types of content that people respond to, see what kinds of content end up as trends, and absorb the overall vibe before producing anything yourself,” Landriscina says.

Users may ask clinicians who post on the app for individual medical advice, Landriscina cautions.

“Keep in mind that answering these requests is not considered ethical,” Landriscina says. “A good way to keep people happy is to see what topics people ask about frequently and produce educational videos about [those topics].”

Landriscina says he was successful on TikTok because he went into it without expectations and to produce content that he likes.

“People can tell if you’re enjoying yourself or not,” Landriscina explains.

It is OK to get a little bit personal, according to Frank, who uses his hobbies, including cooking and roller-skating, in his TikTok videos.

“It’s ok to experiment with different forms of content as long as it’s authentic and true to yourself and your brand,” Frank says. “It’s nice to get a glimpse into someone’s personal life.”

1. Kassamali B, Villa-Ruiz C, Mazori DR, Min M, Cobos GA, LaChance AH. Characterizing top educational TikTok videos by dermatologists in response to “TikTok and dermatology: An opportunity for public health engagement.” 

 2021; 85(1):e27-e28. doi:10.1016/j.jaad.2021.02.051

2. Sehl K. 23 important TikTok stats marketers need to know in 2021. Hootsuite. May 5, 2021. Accessed May 18, 2021. 

3. Szeto MD, Presley CL, Pulsipher KJ, et al. Dermatologist influencers on social media: Instagram Reels and TikTok interactive short videos. 

. 2021;85(3):e185-e188. doi:10.1016/j.jaad.2021.04.052

The app helps dermatologists and aesthetic physicians promote their practices, gain new clients, and share information. 

Inside DermTok: Winning TikTok Strategies

In his 25 years of treating women with hair loss, Alan J. Bauman, MD, ABHRS, FISHRS, says cosmetic physicians should take postpartum hair loss seriously, not only because of its potential cosmetic toll but also because of the emotional burden that comes with hair loss.

“If women say they are losing their hair, 99% of the time they are right,” says Bauman, who has a hair restoration practice in Boca Raton, Florida. “We take the situation seriously, and we more often than not uncover an underlying tendency toward hereditary hair loss which we can evaluate and treat if she desires.”

Common misconceptions about postpartum hair loss, according to Bauman, are that staying on prenatal vitamins will take care of it, there’s nothing patients can do about it, and shampooing less will help.

Hormones often cause postpartum hair loss, according to Jessica A. Shepherd, MD, MBA, FACOG, a board-certified obstetrician-gynecologist, women’s health expert, minimally invasive surgeon, and founder and CEO of Sanctum Med + Wellness, in Dallas, Texas.

“There is a significant shift in the postpartum phase that can lead to changes in how the hair processes, such as when you go through the actual cycle of hair growth. But that is temporary,” Shepherd says. “Patients usually say that they see more of their hair falling out, particularly in the shower, and when they are washing their hair.”

Women often describe postpartum hair loss as a synchronized shedding phase that starts 6 to 12 weeks after childbirth. They complain of decreased hair volume, decreased coverage, and sometimes recession in the hairline and temples, according to Bauman.

What happens to hair postpartum is much different from during pregnancy.

“During pregnancy, due to the effects of hormones, follicles are held in anagen [growth phase], longer, delaying telogen [resting phase]. Therefore, less daily shedding occurs,” Bauman says.

Hormones return to normal after childbirth, and those follicles that were previously in a prolonged anagen phase begin to turn off and hairs begin to shed—a lot—starting about 6 weeks after childbirth and continuing for at least another 2 months, he says.

“This telogen effluvium after childbirth is sometimes referred to as telogen gravidarum,” he says. “Within a few months after pregnancy, a higher percentage of follicles than normal are in the

telogen phase. Regrowth can be slow and some of our postpartum hair loss patients complain of poor hair quality, dull hair, [and] brittle hair.”

However, hormones do not explain all postpartum hair loss.

“There’s also a multifactorial process occurring that includes emotional stress, physical stress, immune response, a healing response, and likely some nutritional gaps that could make this situation much worse for some, especially those who have preexisting conditions like strong hereditary hair loss in the family or genetic traits such as thin, fine, less dense hair [fewer follicles], or a previous history of telogen effluvium, either chronic or acute,” Bauman says.

It is important to reassure patients that postpartum hair loss generally is normal and temporary, according to Shepherd.

“I tell patients hair usually returns to its usual hair growth cycle between 6 and 12 months after birth,” she says.

Postpartum hair loss can take an emotional toll, especially given the changes and stresses after a baby is born. Patients unaware of the possibility of postpartum hair loss might find it shocking or worrisome, Shepherd says.

“Unfortunately, many doctors shrug off female hair loss in general and don’t understand the emotional connection between a woman’s hair and her well-being,” he says. “This is especially true about postpartum hair loss.”

Bauman starts the patient evaluation by taking a thorough history and doing a physical exam.

 and the new AI [artificial intelligence]-driven HairMetrix

 (Canfield Scientific) for a detailed hair growth analysis so we can establish a baseline and monitor over time. We recommend evaluations every 90 days,” Bauman says.

While there are a few treatment options for postpartum hair loss, Bauman says, it is important not to prescribe medications during pregnancy or nursing.

“Nonchemical, breastfeeding-friendly therapy must support the mom’s body and mind, as well as not affect breast milk or the baby,” he says. “Nutrition, self-care, feeling calm, [and] getting rest are all part of the equation. Taking a multitherapy and holistic approach may be preferred.”

As part of his emphasis on self-care, Bauman’s practice offers scalp makeover treatments, performed by a certified trichologist.

“These became exceptionally popular during the pandemic as a safe and relaxing, mentally transporting experience that also helps maintain healthy hair and scalp by addressing scalp inflammation and cortisol levels. A Keravive

 [HydraFacial] exfoliation combined with a scalp massage is therapeutic but also extremely relaxing,” he says.

Nutritionally, since many women continue their prenatal vitamins in the months immediately following childbirth, Bauman says, he is careful not to overdo nutritional recommendations. He recommends supplements, including Nutrafol Postpartum

(Nutraceutical Wellness Inc), which is breastfeeding-friendly, works with prenatal vitamins and addresses the stress/cortisol component of shedding. He also recommends theanine and shatavari, which are herbs and stress adaptogens to help with stress hormones and relaxation, specifically for female physiology, according to Bauman.

At-home laser therapy devices can help, Bauman says. They are nonchemical, noninvasive, and convenient. Plus, today’s options deliver more energy to larger areas of the scalp in less time, he says.

“Avoid weak, clunky-plastic consumer devices and stick to physician-prescribed devices that have over 300 diodes,” he says. “You get what you pay for on this.”

Platelet-rich plasma (PRP) is among the most aggressive of the minimally invasive treatments, and local anesthesia is not an issue for nursing, according to Bauman, who cites a published report in Stem Cell Investigation.

Shepherd, who is unlikely to recommend treatment for postpartum hair loss for up to 1 year after childbirth, says she might recommend PRP if hair loss continues past that point.

“PRP injections are a good avenue because the treatment does not impact moms who are breastfeeding,” she says.

Most importantly, doctors must leave patients feeling reassured that postpartum hair loss will most likely straighten itself out on its own, and give women the time to revert to a normal hormonal status, Shepherd says.

Bauman and Shepherd report no relevant disclosures.

1. Haircheck. Haircheck. Accessed August 9, 2021. http://www.haircheck.com/for-the-trade/ 

2. HairMetrix. Canfield Scientific. Accessed August 9, 2021. https://www.canfieldsci.com/imaging-systems/hairmetrix/

3. The scalp health solution: Hydrafacial Keravive. Hydrafacial. Accessed August 9, 2021. https://hydrafacial.com/keravive/

4. Nutrafol Postpartum. Nutraceutical Wellness Inc. Accessed August 9, 2021. https://nutrafol.com/nutrafol-postpartum-for-women/

5. Garg S, Manchanda S. Platelet-rich plasma-an ‘elixir’ for treatment of alopecia: personal experience on 117 patients with review of literature. Stem Cell Investig. 2017;4:64. Published July 18, 2017. doi:10.21037/sci.2017.06.07

Postpartum hair loss can cause acute emotional burden, according to Alan J. Bauman, MD, ABHRS, FISHRS, and physicians must be aware of the considerations needed for this patient group.

Expert Advice: Don’t Shrug Off Postpartum Hair Loss

 study recently investigated adipose-derived stem cells (ADSCs) for wound healing in an effort to understand their role in both the clinical and regulatory environment.

ADSCs are a form of mesenchymal stromal/stem cells (MSCs). They are heterogenous cells that can be isolated from the stromal compartment of many different tissue types. ADSCs are known to activate local stem cell niches, promoting revascularization, reducing oxidative stress, and modulating immune responses. They can also be harvested in large amounts with minimal donor site morbidity, according to study investigators.

The International Society for Cellular Therapy (ISCT) has created minimal criterial for MSCs:

plastic adherence in standard culture conditions;

expression of CD73, CD90, and CD105 without expression of CD45, CD34, CD19, CD14, CD11b, and HLA-DR surface antigens; and

differentiation into adipogenic, osteogenic, and chondrogenic lineages under appropriate in vitro conditions.

 concluded that MSCs could be used for regenerative cell therapy because of the potential for multilineage differentiation, influence on oxidative stress, and the creation of many soluble mediators that have benefits for the body’s immune system. MSCs from tissues may be closely related to tissue regenerations.

Adipose tissue is a complex endocrine organ that plays a role in energy balance, insulin sensitivity, and inflammation.

 There are 2 types of adipose tissue, white and brown, and although they are derived from the embryonic mesoderm, they are different in location, volume, and function.

White adipose tissue contains mature adipocytes and while they take up over 90% of the tissue volume, the adipocytes are less than 50% of the total cell number. This portion, which includes a mixture of mature, progenitor, and stem cells, must then be separated from the heterogenous cellular population and stromal vascular fraction (SVF).

A crude SVF contains about 30% to 40% ADSCs. These can be isolated in multiple ways such as plastic adherence in culture, Ficoll density gradient centrifugation, erythrocyte lysis buffer treatment, mechanical dissociation, immunomagnetic bead cell sorting, and fluorescence-activated cell sorting, the study investigators wrote.

Challenges of the ADSCs include the way they express specific genes, making them different from MSCs. The consensus position on the ADSC immunophenotype is that the surface antigen expression profile may not meet the minimal criteria for MSC status set by the ISCT, according to the study.

The variability of CD34 expression can make it hard to interpret because of the amount of immunogen subtypes and the choice of antibody may have an effect on signal intensity. There are various ways to isolate ADSC along with different culture conditions that also affect antigen expression profiles. Also, cultured ADSCs are unlikely to represent a completely homogenous population. Heterogeneity can cause issues for quality control.

To resolve these issues, one would identify an ADSC-specific surface marker. However, although there have been attempts to do this, none has been widely accepted. Bone marrow (BM)-MSCs are the most well-defined adult stem cell but ADSCs may be superior for regenerative cell therapies for wound healing. These reasons include ADSCs being less invasive and have been shown to exhibit more marked angiogenic and immunomodulatory effects. Additionally, age is not a factor in the amount of ADSC a patient has.

Currently, only 1 clinical trial has investigated the efficacy of local ADSC administration for cutaneous wound healing, concluding that it does lead to improved wound healing outcomes.

 No clinical wound healing trails using the allogeneic ADSCs have been conducted, but there is potential for off-the-shelf treatment using ex vivo expanded ADSCs for chronic lesions. Of 11 trials using allogeneic ADSCs for applications besides wound healing, there have been no cases of graft rejection, but the full implications of this result are yet to be fully understood, according to the study in 

ADSCs cells promote tissue regeneration with their ability to differentiate into many mesenchymal lineages, though age and gender may play a factor in the efficiency. They may modify target cell behavior by changing the cell interactions and still have an effect even after direct contact is lost.

There is also evidence that MSC conditioned medium (CM) may replicate the effects of MSC wound healing. ADSC-CM has shown to upregulate human dermal fibroblast proliferation, migration, and extracellular matrix deposition in vitro.

Exosomes are an important part of the MSC secretome, and their proteins—mRNA, miRNA, DNA, and lipids—reflect their cell type of origin. Exosomes of MSC upregulate intracellular signaling pathways, which have been proven to have a role in tissue regeneration and may be quantifiable and evaluated for safety, dosage, and potency.

MSC exosomes can be administered allogeneically and stored safety at 68°F without toxic cryoprotective agents, which gives them potential to be manufactured at a commercial scale. MSC exosome therapies may be superior to MSC-CM because of the protection of important molecules from degradation, being stored and delivered in a concentrated form, and the absence of components or supplements not appropriate for human use.

 However, research is still needed to create a better safety and efficacy profile.

The regulatory environment is complicated. In Europe, ADSCs can be treated as cell/tissue therapies or medicines. The US has seen closures of stem cell clinics, along with a statement from the 

FDA Center for Biologics Evaluation and Research

“Stem cell products hold significant potential to improve human health. However, that potential will never be fully realized if careful scientific work and thoughtful clinical investigation supporting the safety and efficacy of these products are not conducted,” according to the FDA statement. “The FDA is committed to helping advance the safe and effective development of novel stem cell products. We look forward to working with those who share our goal of bringing safe and effective products to market to benefit individuals in need.”

The regulatory environment worldwide is taking a closer look at the therapy. The Royal Australian College of Surgeons, in 2016, noted that the Therapeutic Goods Administration saw a huge uptick in the number of autologous stem cell treatments, but at that time, there was no evidence to support their effectiveness and while it prompted a review, the review remains unpublished.

After 3 cases of women being blinded by stem cell injections intended to treat macular degeneration8, and the FDA’s decision to close many stem cell clinics, there may be pressure to follow its lead.1 The FDA released 2 guidance documents related to stem cell treatment, 1 to clarify the “same surgical procedure”

 and the other concerning the definitions of “minimal manipulation” and “homologous use.”

“We have to do all of the safety studies and truly make it into an investigational new drug application [NDA]. The problem with that is that every time we use somebody’s stem cells, it’s a new drug every time and the expense of doing a new drug [application] every time is exorbitant,” explains Jack Zamora, MD, Cosmetic Surgery and Aesthetics, Denver, Colorado.

The FDA guidance for “homologous use” highlighted the importance for the anticipated function of the cells, not just the anatomical site of application. The FDA gave the example of using adipose tissue for contouring a soft tissue defect as homologous use, as cushioning and support are the basic functions of adipose tissue. However, using adipose tissue for cartilage or tendon repair, according to the guidance, is nonhomologous because tissue regeneration and immunomodulation are not basic functions of adipose tissues, according to the current scientific consensus.

The 361 product designation is defined as a minimally manipulated product, such as placental tissue or umbilical cord tissue. It can be prepackaged with FDA good manufacturing standards (GMS) and premarket approval is not needed, according to Zamora.

361 products that meet all the criteria outlined in 21 CFR 1271.10(a) are regulated as human cells, tissues, and cellular and tissue-based products (HCT/Ps) and are not required to be licensed or approved by the FDA; they are instead regulated by Section 361 of the Public Health Service (PHS) Act.

However, the issue is that these products are not as pure as they could be because among the stem cells are red and white blood cells, the inclusion of which can cause immune reactions. Another issue is how well each company is sticking to the GMS set by the FDA and making sure the tissue has not been infected, Zamora said.

There are 351 designations that do not meet all the criteria of a 361 product and are considered investigational new drugs. Through 

, Zamora has helped launch a phase 1-11a, randomized, double-blind, placebo-controlled study on the safety and efficacy of therapeutic treatment with AlloRX Stem Cells in adult patients diagnosed with COVID-19.

“COVID-19 has opened the door for stem cells to be used in the [United States] legally,” Zamora says. “We’ve already treated patients around the [United States] with IV stem cells under the emergency order for COVID-19.” Zamora says he thinks we could see widespread stem cell use in the US in less than 10 years.

Cell therapies are likely to increase the importance of regenerative wound healing and regulation will increase accordingly. This will likely lead to a change in the way current cell treatments are delivered, and regulation is as much an opportunity as it is a threat, as is having pathways to approval in place and advice for researchers available, Zamora says. Additionally, more research is needed.

“I think the FDA is doing what they’re supposed to do,” Zamora says, noting that the FDA has a responsibility to help those who are not sick and prevent them from becoming sick from any FDA-regulated products. Additionally, it’s important to stop those who may have gotten sick from these products from becoming increasingly ill.

Luck J, Weil BD, Lowdell M, Mosahebi A. Adipose-derived stem cells for regenerative wound healing applications: understanding the clinical and regulatory environment. 

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Strioga M, Viswanathan S, Darinskas A, Slaby O, Michalek J. Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. 

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Majka SM, Barak Y, Klemm DJ. Concise review: adipocyte origins: weighing the possibilities. 

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Peirce V, Carobbio S, Vidal-Puig A. The different shades of fat. 

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Najar M, Rodrigues RM, Buyl K, et al. Proliferative and phenotypical characteristics of human adipose tissue-derived stem cells: comparison of Ficoll gradient centrifugation and red blood cell lysis buffer treatment purification methods. 

. 2014;16(9):1220-1228. doi:10.1016/j.jcyt.2014.05.021

Marino G, Moraci M, Armenia E, et al. Therapy with autologous adipose-derived regenerative cells for the care of chronic ulcer of lower limbs in patients with peripheral arterial disease. 

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Bhang SH, Lee S, Shin JY, Lee TJ, Jang HK, Kim BS. Efficacious and clinically relevant conditioned medium of human adipose-derived stem cells for therapeutic angiogenesis. 

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McGinley L. Three women blinded by unapproved stem-cell ‘treatment’ at South Florida clinic. 

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https://www.washingtonpost.com/news/to-your-health/wp/2017/03/15/three-women-blinded-by-unapproved-stem-cell-treatment-at-south-florida-clinic/

US Food and Drug Administration. Same Surgical Procedure Exception under 21 CFR 1271.15(b): questions and answers regarding the scope of the exception. November 2017. Accessed July 22, 2021. https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Same-Surgical-Procedure-Exception-under-21-CFR-1271.15%28b%29-%C2%A0Questions-and-Answers-Regarding-the-Scope-of-the-Exception.pdf

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In an Aesthetic Surgery Journal study, adipose-derived stem cells are examined in regard to their role in regenerative wound healing and how today’s regulatory environment is revolving around them.

Adipose-Derived Stem Cells for Wound Healing

Most reported adverse events (AEs) associated with cryolipolysis (CoolSculpting; Allergan) treatment are minimal and transient. But there are a handful of potentially serious complications from the popular noninvasive body contouring option.

The most common and relatively mild AEs of erythema, numbness/paresthesia, bruising, and edema are to be expected from a technology that freezes subcutaneous adipose tissue, according to Bobak Hedayati, MD, dermatology resident at University of California (UC) Irvine and first author of a systematic literature review of cryolipolysis-associated AEs published last year in 

In the review, the less-serious common AEs developed within a week of treatment and resolved spontaneously, according to the authors.

“The meat of our study was to look for those uncommon or rare complications that are possible,” Hedayati says.

In their review of 53 articles and a total 3,312 cryolipolysis patients, Hedayati and colleagues found the more serious AEs (SAEs) associated with cryolipolysis were: dysesthesia—including increased sensitivity, tingling or burning in 59 patients—delayed, severe, or persistent pain in 49; paradoxical adipose hyperplasia in 30; skin blanching in 15; vasovagal reactions in 14; skin hyperpigmentation in 8; and contour irregularities in 3 patients. Nerve injuries also occurred in some patients.

A Closer Look: Paradoxical Adipose Hyperplasia

Less than 1% of cryolipolysis patients develop paradoxical fat hyperplasia, an unexpected increase in the number of fat cells, according to the American Society of Plastic Surgeons website.

Paradoxical fat hyperplasia is three times more common in men than in women and is seen more in those of Hispanic or Latino descent, according to the American Society of Plastic Surgeons.

“This is a serious complication in the sense that it does not go away on its own,” Hedayati says. “It is a benign tumor of the fat cells. All the cases in our review had to be treated with liposuction.”

There is evidence that some patients with paradoxical adipose hyperplasia resolve without treatment, according to a 2018 paper published in 

 Investigators studied 398 patients who each had a session of cryolipolysis, 4 of which presented with voluminous painless swelling in the treated area between 2- and 4-months posttreatment. While 1 patient was treated with liposuction, the other 3 did not receive any additional treatment and their symptoms stabilized after several months, according to the authors

 of nearly 8,700 cycles of cryolipolysis in 2,114 patients, investigators reported paradoxical adipose hyperplasia incidence rates of 0.05% to 0.39%. However, incidence rates fell by more than 75% with new CoolSculpting units, according to the 2021 paper.

 Italian investigators reported that transitioning from the CoolSculpting CoolCore system to the CoolAdvantage applicator system had no impact on safety but led to greater versatility and increased numbers of cycles per treatment.

“There were only 2 significant complications: 1 paradoxical adipose hyperplasia (with CoolCore) and one loss of sensation (with CoolAdvantage),” the authors wrote.

Some suggest paradoxical adipose hyperplasia can result from improper use of the device—not freezing an area long enough or not latching on well enough to the treatment site to achieve adipose tissue apoptosis, according to Hedayati.

Nerve injuries post-cryolipolysis are also more likely to occur with improper or inappropriate use of the CoolSculpting device, says study author Margit Juhász, MD, MSc, a dermatology resident at UC Irvine.

“It’s very rare to have nerve pain or numbness that lasts for more than a week after cryolipolysis,” Juhász says.

study included a case where a patient treated with CoolSculpting on the upper arm developed a radial nerve injury leading to weakness in the wrist and finger extension. The patient’s motor function was restored 6 months later with no additional treatment.

One possible reason for the complication, according to Hedayati, was the patient was thin and might not have had enough adipose tissue on the arm to indicate cryolipolysis.

“The radial nerve runs pretty superficially to the skin, so a skinnier person may have a higher risk of damaging those superficial nerves,” she says.

Additional complications written in the review included separate patients reporting left mandibular nerve injury, throat swelling, and hoarseness after submentum cryolipolysis.

Post-inflammatory hyperpigmentation from cryolipolysis occurred from 2 days to 3 months after treatment and resolved in 7 of the 8 patients within a year. There was 1 report of unresolved skin hyperpigmentation that lasted more than a year and was treated with nonablative laser therapy, according to the review.

When used incorrectly or inaccurately, cryolipolysis can, in rare cases, result in SAEs including dysesthesia, pain, paradoxical adipose hyperplasia, skin blanching, vasovagal reactions, skin hyperpigmentation, contour irregularities, and nerve injuries.

Innovative Perspectives: Aesthetic Authority Vol. 2: No. 3

Innovative Perspectives: Aesthetic Authority Vol. 2: No. 3

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Expert Advice: Don’t Shrug Off Postpartum Hair Loss

Adipose-Derived Stem Cells for Wound Healing

Rare Cryolipolysis Complications

Single-Plane vs Double-Plane MFU-V for Upper Arm Skin Laxity

Is NPS effective for facial treatment?

Marine Collagen—Safe and Effective for Skin Rejuvenation?