Autologous adipose tissue injection in the treatment of alopecia: A mini‐review

Alopecia may decrease patients' quality of life and self‐confidence by limiting their social life. Therefore, the main goal of the treatment is to limit or halt the progression of inflammation, scarring, and hair loss. The promising effect of fat injection on hair regrowth, limited adverse effects, and subsiding inflammation can be proof of its efficacy and safety in treating alopecia.


| INTRODUC TI ON
Hair loss, or alopecia, is a debilitating skin disease that causes a significant impact on the attractiveness and appearance, self-esteem, and life quality of patients. 1Alopecia is broadly categorized into scarring (cicatricial) and non-scarring subtypes. 2Non-scarring alopecia is reversible, and hair follicles are preserved, which makes hair regrowth possible.Androgenic alopecia (AGA), alopecia areata (AA), telogen effluvium, anagen effluvium, traction alopecia, trichotillomania, and alopecia syphilitica are common types of non-scarring alopecia.Cicatricial alopecia (CA) is characterized by the destruction of the hair follicles and their subsequent replacement with fibrosis through inflammatory processes, resulting in irreversible hair loss. 3There are two main types of CA: primary and secondary.In primary CA, the permanent portions of the hair follicles are affected and destroyed by inflammation.
Lichen planopilaris (LPP) and its other variants, frontal fibrosing alopecia (FFA) and Graham-little-piccardi-lasseur syndrome (GLPLS), pseudopelade of brocq, central centrifugal CA (CCCA), and Folliculitis decalvans (FD), are classified as primary CA.The hair follicle in secondary CA is merely a bystander to the illness process rather than its primary target.The causes of secondary CA include congenital, autoimmune, and inflammatory diseases; physical and chemical injuries; infections; ionizing radiations; malignant and benign tumors; and drugs. 4curate diagnosis of alopecia and starting an optimal treatment are of great significance in medical practice, as the condition is underestimated in most cases. 5Hair transplantation (HT) for LPP and FFA seems feasible to treat alopecia. 6Other novel methods are microneedling, 7 mesotherapy, 8 and laser-assisted hair regrowth, which reports significant hair regrowth.In addition, sonophoresis, ionophoresis, and nanoparticles are current novel approaches for hail loss treatment. 9The available treatment tools have their own benefits and limitations, and therefore, alternative therapies and novel therapeutic approaches are always sought.
Human adipose tissue (AT) is a rich source of stem cells and multiple growth factors that has been widely used for cosmetic purposes, such as facial rejuvenation and volumization. 10Various types of cells are present in AT, including adipocytes, endothelial cells, adipose-derived stem cells, mural cells, fibroblasts, and leukocytes. 11Adipose-derived stem cells are multipotent cells and have the ability to differentiate into mesenchymal lineage cells. 12ditionally, several growth factors were monitored to be secreted by adipose-derived regenerative cells (ADRC), 13 and the effectiveness of ADRCs in hair growth was reported in multiple studies. 14e of the unique characteristics of AT cells is their ability to induce angiogenesis, which theoretically supports the efficacy of ADRCs in treating alopecia.Furthermore, AT has anti-inflammatory and anti-oxidative agents, preventing further damage to hair follicles in inflammatory disorders of the scalp.Obtaining stem cells from AT is simpler than from bone marrow, making this method ideal for stem cell harvesting. 15de effects following long-term systemic therapies enhance the need for evaluating and introducing new therapeutic modalities.Therefore, the promising effect of AT injection in treating alopecia, lacking systemic adverse effects, having favorable hair regrowth results, and subsiding the inflammatory process prompted us to conduct the current review, evaluating the effect of autologous AT injection in the treatment of different types of alopecia.

| ME THODS
A thorough search was performed on the Web of Science, Scopus, and PubMed/Medline databases, as well as the Google Scholar search engine for studies published from inception until September 1st, 2023, using the related keywords, and a total of 10 case series and case reports were found.

| RE SULT AND D ISCUSS I ON
All characteristics of the included studies are summarized in Table 1.

| Scarring alopecia
AT injection in the treatment of alopecia is a relatively novel modality.A case series of nine patients with LPP-induced alopecia revealed the significant efficacy of autologous AT transfer only after one session.The treatment improved hair density and diameter, as well as LPP-induced inflammation, scaling, scalp, and perifollicular erythema.In addition, improvements in the hair-pull test and lichen planopilaris activity index (LPPAI) scores were also reported. 16Moreover, Tedesco et al. reported a case of recurrent FD that was unresponsive to conventional treatments. 17

Key points
• Due to the substantial risks and huge burden associated with alopecia, its proper treatment is of the utmost importance.
• The adipose-derived regenerative cells in adipose tissues can secrete various growth factors and induce hair regrowth in alopecia.
• Autologous adipose tissue transfer can be considered a novel and potentially effective treatment method for hair loss and alopecic conditions.Several studies have evaluated the effect of autologous AT injection in various clinical conditions; trauma can cause alopecia, which seems to have a negative impact on one's life.AT injection showed considerable potential for hair regrowth in the treatment of post-traumatic alopecia.It is also the easiest and safest approach to a source of mesenchymal stem cells, which seems to be the main cause of hair regeneration in the treatment mentioned above. 18other study also demonstrated the effectiveness of autologous fat grafting (AFG) in treating scars and trauma-induced alopecia by combining HT (mustache transplantation) and AFG to camouflage post-surgical cleft lip scar.The patient and observer scar assessment scale (POSAS) score was 6.7 before fat grafting, 5.3 before HT, and 3.2 at 12 months after the treatment, showing a significant improvement. 19In addition, hirsutism induced by AFG was reported in a study on a 60-year-old female after facelift surgery accompanied by AFG to both cheeks.A month after the surgery, excess hair growth on both cheeks was observed. 10Unlike the mentioned studies, alopecia was reported following the autologous fat injection into the temporal area in another report: a 36-year-old woman with progressive and linear temporoparietal hair loss following AFG for facial augmentation. 20tologous fat transplantation can be combined with other proper modalities in the treatment of alopecia.In a study conducted by Epstein et al. 15 pretreating scars on the scalp with autologous AT injections before HT resulted in favorable outcomes in a patient with chemical injury in the temporal regions.As a result of the addition of AT to recipient sites, the scar tissue would typically bleed more than untreated scar tissue during the creation of new recipient sites for hair grafts.This indicates the angiogenetic property of AT, which has a notable role in hair regrowth.Epstein et al. also studied the role of autologous fat transfer with platelet-rich plasma (PRP) to treat alopecia; however, PRP alone has demonstrated beneficial effects in the treatment of different forms of alopecia. 21The combination of AFG and PRP showed significant hair regeneration and a reduction in further hair shedding in patients. 15me studies reported the effects of fat injection in other disorders and the treatment of their consequences.Scleroderma is a disorder with potential hair loss outcomes.In patients suffering from scleroderma, linear skin depression, and an atrophic alopecic patch, treatment with autologous fat transplantation on the involved area showed a significant clinical improvement in both the linear depressed atrophic scar and the depressed alopecic patch. 22Adipose tissue-derived stem cell therapy was also applied to treat other clinical presentations of scleroderma, mainly the vascular manifestations.Following the autologous fat transplantation, a significant improvement was reported in hand disability and pain, Reynaud's phenomenon, finger edema, and quality of life. 23The therapeutic effect of Adipose tissue-derived stem cells can be explained by their ability to promote vasomotor tone, microvascular perfusion, vascular repair, and angiogenesis.Thus, AFG can be considered a potential treatment alone or combined with other modalities for individuals suffering from scleroderma.

| Non-scarring alopecia
Although CA can be difficult to treat, non-scarring forms of alopecia can also be challenging and have negative effects on patients' A 26-year-old female patient with linear skin depression and atrophic alopecic patches was treated with AFG for two sessions at 3 months interval.Adipose tissue was harvested from the patient's buttocks with Klein's solution using a 10-mL Luer lock syringe and a blunt 14-G cannula 2 mL of fat was injected at the hairline and 0.5 mL was injected to the forehead in the first session.1 mL was given 3 months after using frozen fat Abbreviations: AA, alopecia areata; ADRC, adipose-derived regenerative cells; AFG, autologous fat grafting; AGA, androgenic alopecia; AT, adipose tissue; CA, cicatricial alopecia; FD, folliculitis decalvans; FFA, fibrosing alopecia; GLPLS, Graham-little-piccardi-lassueur syndrome; HT, hair transplantation; LPP, lichen planopilaris; LPPAI, lichen planopilaris activity index; NA, not applicable; POSAS, patient and observer scar assessment scale; PRP, platelet-rich plasma.
TA B L E 1 (Continued) lives. 24AFG appeared to be effective in treating non-CA as well; AGA is a common non-CA that showed desirable hair regeneration results following autologous AT injection.However, to maintain the results, re-treatment at specific intervals is required to be considered. 25Furthermore, hair regrowth in a patient with alopecia universalis, a form of non-CA, was also observed in a study after 6 months of treatment with AFG, supporting the potential of ADRCs. 15AFG was also efficacious in AA, which is an autoimmune condition inducing patchy hair loss. 26In addition to the remarkable improvement in the atrophic scar that was caused following unsuccessful treatment with triamcinolone acetonide injection, hair regrowth was noticed 3 months after the lipofilling.The existing evidence suggests that AFG can be promising for non-scarring alopecia as well.

| Safety and treatment response
Adverse effects following AFG were not serious and primarily included self-limiting bruising, small hematoma, mild to moderate pain at the site of liposuction, and mild to moderate burning and pain at the site of scalp injection.In all reviewed studies, favorable results were explained based on ADRCs, growth factors release, antiinflammatory/anti-oxidative activity, as well as angiogenesis, which increases blood and nutrient flow into the injection site.Based on these changes followed by AFG, this modality can be utilized for cosmetic purposes, including scars and alopecia or other disorders involving the skin, such as scleroderma.
In addition to the type of alopecic condition, the difference in AFG methods in the studies can explain the outcome.Previous investigations have shown the importance of regenerative MSCs and preserving adipocyte integrity with minimal injury and manipulation in treatment results. 27In a study comparing three types of fat-processing techniques (decantation, washing, and centrifugation), the percentage of intact nucleated adipocytes was remarkably higher in decanted lipoaspirates, while centrifuged samples contained more altered adipocytes.Also, a significantly higher concentration of MSCs was detected in washed lipoaspirates compared to samples that had been decanted or centrifuged.Hence, washing was found to be the best method for processing AT graft due to its ability to maintain adipocyte integrity and number, remove blood contaminants, and contain a large number of endothelial cells and MSCs.
Besides, in another study, three different centrifugation forces (Coleman's technique with centrifugation at 3000 rpm for 3 min, centrifugation at 1300 rpm for 5 min, and simple decantation) on fat aspirates were evaluated. 28The results indicated that a centrifugal force of 1300 rpm maintained a notable count of progenitor cells and had good cell viability and AT density.Additionally, the volume of the injected fat, the detail of the procedures, and the number of sessions can affect the treatment response that needs to be investigated in the studies.

| Limitations and recommendations
There is scarce evidence regarding the treatment of alopecia, both cicatricial and non-cicatricial, with AT injection, discussing the number of treatments, intervals between sessions, and relapse of the disease.Hence, further studies, mainly clinical trials with larger

Safety and adverse events
Patients' satisfaction Recommendation POSAS, clinical evaluation Scar improvement was statistically significant 12 months after the treatment, acceptable graft survival rate (73.6%-88.6%),and density success per cm Fattransfer offered huge potential in hair generation as it led to hair regrowth in the peripheral area and diminished new folliculitis formation in the patient.

TA B L E 1
Characteristics of eligible studies on autologous fat injection in the treatment of alopecia.45-50 with alopecia due to chronic LPP received a single treatment session of autologous adipose tissue transfer and were followed up every 3 months for a year.The patients received local anesthesia and tumescent fluid injection in their upper part of the lateral thigh.After 20 min, adipose tissue was aspirated using a 2.4 mm harvesting tulip cannula into a 20 mL syringe from the same location.Then, the entire 20 mL of adipose tissue was injected into their scalp on the same day 20 mL of adipose tissue injected with an 18-gauge insulin syringe into the scalp (1.0 mL/cm 2 ) after desensitizing with Lidocaine 2%/1:200 000 epinephrine and subcision of fibrosis with blunt technique Nilforoushzadeh, 2021 28 Case series AGA Nine adult patients: 5 women and 4 men with AGA received 20 cc autologous whole fat three times at 3-month intervals.Adipose tissue was aspirated from the lateral upper thigh using a 2.4 cannula into the 20 mL Luer lock syringe, then left for 10 min to let the excess fluid separate from the fat 20 mL of adipose tissue 1.0 mL/cm with scars and alopecia in the cleft lip area.Fat aspirated from the periumbilical region by means of miniature liposuction harvesting cannulas.hair transplantation was performed with hair from the submental area and scalp using the folliculate unit extraction technique 3 months after transferring fat 1-2 mL of adipose tissue grafted under the scar tissue using a 17-gauge Coleman cannula Dini, 2014 29 Case report AA of eyebrow A 26-year-old female patient received one session of AFG. 3 mL of fat was harvested using a 10 mL Luer lock syringe, a 0.9 blind Tulip cannula and Klein solution 0.5 mL of purified adipose tissue was injected into the left eyebrow