More than filling alone?

During the last century, it became apparent that multipotent or precursor cells were available in subcutaneous fat36. However, harvesting and classifying these cells proved to be a technical challenge. The introduction of liposuction changed all this and for the first time there was access to large volumes of living human fat cells. Zuk et al3 showed that this was indeed the fact, and their findings led to significant advances in stem cell related tissue engineering and regenerative medicine. The ADSC almost has the same differentiation as other stem cells37, but are readily available and easy to access38.

With the introduction of superficial lipofilling in plastic surgery, clinical observations soon followed. Coleman, in 200612, was one of the first to suggest that ‘lipofilling might be more than filling alone’ and could have a local rejuvenative effect. In a number of cases of lipofilling of the face, the overlying skin showed some changes; small wrinkles disappeared, pore size decreased, and pigmentation improved. Also, scars seemed to fade and felt more like ‘normal’ skin (Figure 5).

These first observations led to the initiation of studies that evaluated these rejuvenating properties. In 2007 Rigotti et al30, in their study Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells, introduced a new method in treating irradiated skin. For the first time, lipofilling was used as a therapy to repair the damaged skin instead of using it for volumetric correction. Rigotti suggested that the positive rejuvenating effect reported in the study might be attributed to the ADSCs present in the lipograft.

More recently, Sultan et al39 showed a similar finding in a placebo-controlled animal study. Mice underwent radiation, with one group receiving lipofilling of the damaged area, and one group a placebo. Lipofilling dampened the effects of the acute radiodermatitis. An observation that was further supported by histological findings: there was less fibrosis and SMAD3 expression (fibrosis marker). The authors suggest that these effects might be owing to the ADSC, either by neo-angiogenesis or inhibiting the TGF-β myofibroblast.

Figure 4 A 24-year old woman with evident breast asymmetry; (A) pre-operative, (B) 4 months postoperative after 320 cc of lipofilling and the BRAVA system, (C) 14 months postoperative, after gaining weight (4 kg) both breast increased equally in size.

Figure 4 A 24-year old woman with evident breast asymmetry; (A) pre-operative, (B) 4 months postoperative after 320 cc of lipofilling and the BRAVA system, (C) 14 months postoperative, after gaining weight (4 kg) both breast increased equally in size.

The regenerative properties of the lipograft was soon used for other types of skin damage, such as thermal injuries. Klinger et al40 were the first to present a small case series (n=3) that were treated with lipofilling after hemifacial second and third degree burns. Klinger concluded that, ‘lipofilling improves scar quality and suggests a tissue regeneration enhancing process’. The group of Sultan et al41 also conducted a placebo-controlled mice study that explored the possibility of using lipofilling to minimise scarring after thermal injury. The mice that received lipofilling directly after administering the thermal injury showed increased neoangiogenesis of the area, measured with a duplex Doppler, and cellular expression of related genes. Also, as with the irradiated mice, a lower amount of fibrosis was observed in the lipofilling treated mice. The authors suggest that the ADSC might take over or assist the endothelial progenitor cells, which are paramount for neoangiogenesis after thermal injury. It is widely accepted that with severe thermal injury, the endothelial progenitor cells response from the bone marrow is slow, or even absent42. The resulting hypoxic tissue will result in a high TGF-β expression that results in severe scarring. Lipofilling might have a place in treating thermal injuries in the future.

Another application for the regenerative properties of the lipograft was presented by Cervelli et al43,44. In a number of pilot studies they show the treatment of post-traumatic and chronic ulcers with a combination of PRP and enhanced stromal vascular fraction lipografts (or ADSC enriched). According to Cervelli et al, the clinical results are good, with high patient satisfaction. Unfortunately, the number of available studies that research this treatment is low. It may well be that this therapy will form an alternative to extensive debridement followed by loco-regional reconstruction or hyperbaric oxygen therapy.

Further research into the cellular interactions between the ADSC and adipocyte, along with the interaction of the ADSC on the local cellular environment will give insights into the reported regenerative effects and lead to new therapies. Most likely, fat graft survival will increase, as well as in bad donor areas like irradiated tissue. Also, tissue engineering with the use of ADSC and scaffolds37 (3D Matrix) is showing great potential both in-vitro45 and in-vivo46. Furthermore, the down-regulating effect of the ADSC on the immune response might be a future therapy for scar prevention, revision, and chronic inflammatory skin diseases. Anecdotally, during the last 3 years the senior author of this article has used superficial lipofilling with PRP successfully for skin rejuvenation of the face, décolletage, and hand dorsum. A blind randomised controlled trial is currently underway to further objectify these findings.

Table 2

Oncological safety of lipofilling

The potential carcinogenic properties of lipofilling has been a point of discussion in many articles. Fundamental studies show that adipocytes placed in hypoxic condition produce large amounts of VEGF and other proliferative growth factors47,48. Furthermore, the aromatase available in adipocytes results in a high local oestrogen concentration48. If we take into account that the vascularisation of breast tissue is relatively poor in comparison to the face, both factors have the potential to be a carcinogenic trigger.

In the recently published systematic review by Claro et al49 on oncological complications after lipofilling of the breast, the number of mammographic changes were comparable to other forms of reconstructions. However, the number of level one and two trials included in this review was low. The ability to detect changes early in a mammography are not influenced by lipofilling in that breast50. The British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) recently updated their guidelines. These updates included: lipofilling is a good alternative for breast reconstruction51, and follow-up can take place according to the standard guidelines for oncological breast reconstruction. The US guidelines are less progressive and give no recommendation, but do say that lipofilling is ‘promising and clinically relevant’2. Further studies with adequate power and long-term follow-up are required to draw definite conclusions. In addition, little is known about the role of additives like PRP or ADSC enrichment on the oncogenic potential of the lipograft.

Figure 5

Lipofilling in daily practice

Table 2 shows an overview that could serve as a guideline for the aesthetic and reconstructive surgeon. The experience of the surgeon and his operating team, as well as the expectations of the patient, are important factors in achieving a satisfying result, which sometimes requires multiple procedures. Clinical results are presented in Figures 3–4.

Conclusions and future expectations

The use of living fat cells for reconstructive and aesthetic purposes, harvested and grafted to a donor site within the same individual looks more promising than ever before. The lack of significant level one and two trials is a reason to be reserved at this time. Lipofilling not only seems interesting for the reconstruction of volumes, but also the regenerative potential of the ADSC allows for reconstruction on a cellular level. The technological advances and practical improvements of the last decade makes lipofilling a good or even better alternative than current treatments options. Many other clinicians, such as dermatologists, interventional radiologists, and cardiologists52 have shown their interest in lipofilling — especially in the regenerative potential of the lipograft. This article’s two authors have initiated a number of studies, including a randomised controlled trial and fundamental studies into the effect of PRP on the lipograft.