Franz Neuber first published his work on autologous fat transplantation back in 1893, but it was not until the 1980s that fat transfer started to make waves. With the advancement of liposuction techniques, plastic surgeons saw discarded fat as somewhat of a treasure. By purifying the extracted fat and re-injecting it back into specific areas, plastic surgeons were able to contour breasts, plump shrivelled hands, restore volume to sunken cheeks, boost one's buttocks, and many more.

This seemed like an innovative substitute to synthetic fillers and implants, which had their own set of drawbacks such as rejection (implants) and frequent repeat treatments (fillers). Even patients preferred the idea of sucking out fat from unwanted areas and putting it in areas where they need it more, without running the risk of rejection or an allergic reaction.

However, as exciting as this new method was, one challenge remained - how to refine the technique so that the fat cells would efficiently survive in a new site after transplantation, thus serving as a ‘natural' filler. Back then, no one would have thought that a possible answer would come from stem cells, which are found, predominantly, in every multi-cell organism. How stem cells naturally behave sets them apart from other cells.

Singaporean plastic surgeon Dr Woffles Wu explains, ‘Stem cells are precursors of adult mature cells. They are thought to have the ability to differentiate into new tissues, which may not be their original cell line. For example, it is thought that if stem cells are placed in an area of trauma like bone loss, it may regenerate new bone cells.'

Today, we know that the human body is a vast reservoir of stem cells. Medical science has long paved the way in stem cell research, from identifying stem cell domains in our body to harvesting them from certain sites - namely human embryos, peripheral blood, bone marrow, umbilical cords, placentas and the current headliner, fat tissues.

Stem cells harvested from fat tissues are called adiposederived stem cells (ADSC) and are a valuable discovery, especially to the world of regenerative and aesthetic medicine. ‘There is an easy and convenient supply - a plentiful supply - of fat in the body, and it just so happens that the fat in the body is very rich in stem cells,' explains Dr Wu.

Fat: from most unwanted to most wanted

‘The potential for possible therapeutic uses of stem cells in replacing dead cells or organs and in regenerative medicine has created much enthusiasm and many expectations,' says Dr Peter Wong, Malaysian plastic surgeon and current president of the Malaysian Association of Plastic, Aesthetic and Craniomaxillofacial Surgeons (MAPACS). ‘Plastic surgery is no exception. Of particular interest, is ADSC,' he says.

Autologous fat transfer procedures have grown in popularity since the 1980s, but survivability of the transferred fat remained far from satisfactory. This spurred researchers worldwide to combine their expertise to determine how transferred fat lasts in a new location, leading them to focus on ADSC for many reasons.

Prior to ADSC, the survival of aspirated fat that is reintroduced into different areas of the body depended primarily on a good grafting technique to induce revascularisation (restoration of the blood circulation) and angiogenesis (growth of new blood vessels) - without adequate blood supply, the cells do not receive sufficient oxygen to survive.

Additionally, it was also found that to boost survival rate, fat cells needed to be purified and separated from other cellular debris including blood, connective tissue and other biological substances through centrifugation before being re-introduced into the body. On top of that, it is crucial that the extracted fat tissues are not exposed to the external environment throughout this whole process so as to avoid any risk of contamination. All this had to be done manually and in various stages.

Early centrifugation methods for fat purification were unpopular because it was technique-dependant; each plastic surgeon would get a different result depending on the way the separation of the fat cells was carried out. But with the advent of an automated machine like Lipokit, fat transplantation saw a brighter future. South Korean plastic surgeon and Lipokit creator Dr Hee Young Lee explains, ‘Lipokit is an all-in-one integrated closed system that can perform all the fat transfer procedures through this one machine - liposuction, centrifugation, harvesting and fat transplantation.'

Because the process is accomplished in a closed infection-free environment, survivability of the transferred fat cells is raised from 30 to 40 percent (in manual fat grafting) to 90 percent - a big and encouraging leap to surgeons. But there remained one more issue.

Only 200cc of fat can be harvested at one time, and only a small amount - 25cc to 40cc - of purified fat can be obtained. This small yield is deemed highly precious and, therefore, ensuring survivability of these fat cells became even more crucial. Enter ADSC.

A fat chance in survivability...

‘The key advantage is that ADSC can help transferred fat survive longer, attach to its new transplanted site better, and increase tissue longevity by improving blood supply,' states Associate Professor Ivor Lim, Singaporean plastic surgeon and stem cell researcher. Fat grafts that survive can remain at the implanted site permanently, therefore outlasting any synthetic filler, which usually require follow-up treatments after a certain number of months. Additionally, as the cells are extracted from the patient's own fat, there is no concern of an allergic reaction.

‘ADSC is now generally accepted to play a key role in delivering successful fat graft results,' says Dr Wong. ‘There is much hope that, with further understanding and research, autologous fat grafting will be safe, reliable and acknowledged as the prime volume filler in body contouring and regenerative medicine.'

Researchers have substantiated that the fat tissues have a relatively high density of pluripotent cells (stem cells that are able to differentiate into many types of cells) while studies on ADSC underlined the ease with which they achieved multi-potentiality (degree of differentiation), their self-renewal potentials and their elevated levels of angiogenesis. Additionally, ADSC also share a unique trait with other stem cells. ‘ADSC have powerful "chaperone effects", whereby they somehow trigger repair mechanisms in surrounding cells when they are placed in damaged tissues,' highlights Dr Lee. ‘It would be ideal to simply inject ADSC into parts of the body we wish to regenerate and let them do their job.'

Associate Professor Lim's account also supports this bonus feature. ‘ADSC-enhanced fat grafts also present better results. For instance, after ADSC-enhanced fat graftings, overlying skin at surgical sites is tauter and more elastic,' he assures. He adds, ‘A very important fact is that ageing is stem cell failure. When stem cells no longer work to replace and renew cells, we age.'

But there is a catch - isolating stem cells from fat tissues can be tricky. ‘While plastic surgeons have been able to extract fat, purify it and inject it back to patients, we have not been able to isolate the stem cell fractions. And this, of course, requires a laboratory technician and researchers who are familiar with the techniques,' says Dr Wu.

Fortunately, plastic surgeons might now be able to overcome this hurdle with Maxstem. Another brainchild of Dr Lee, Maxstem works hand-in-hand with Lipokit to isolate ADSC and phase it back into harvested fat to dramatically maximise its survivability. Condensed fat from the Lipokit is first siphoned into Maxstem before a series of chemicals are used to ‘wash' the fat and isolate its stem cell fractions. The fractions are then laced back into the remaining condensed fat before grafting.

With the dynamic duo of Lipokit and Maxstem, fat grafts and ADSC isolation is stepping into a new frontier. Add to that the fact that Lipokit and Maxstem are quite easy to operate. Dr Lee says, ‘A trained nurse can isolate ADSC, in the operation room itself, and transfer it to the patient in one procedure.'

Dr Wu, user of both machines, also shares Dr Lee's sentiments. ‘These two machines have shortened and simplified what used to be a complicated laboratory-based endeavour - they more or less brought the lab into the plastic surgeon's clinic.'

Taboos, issues and future news

Harvesting stem cells from fat is, ethically and technically, a less complicated endeavour than obtaining stem cells from other parts of the body. Every year, through countless liposuction procedures around the world, unwanted fat is disposed of by the hundreds of litres. Dr Wong notes, ‘There does not seem to be any taboo on the use of fat stem cells, particularly as it is autologous.'

But as the potential of ADSC remains uncharted, potential risks must be identified and prevented. ‘There are risks but what specifically the experts don't know yet, and hence we must be careful,' says Dr Wu. ‘The field is in an experimental stage so we have to tread with caution, proper scientific basis and good ethical judgment. Doctors should not over-promise or exaggerate the claims about what stem cells can or cannot do. It is best to set up more clinical trials and studies so that individuals will not be exposed to the risks,' he adds.

Although many still cannot determine all the benefits and risks that are associated with fat grafting using ADSC, experts have a good idea about the direction in which fat grafting is heading.

‘In the future, techniques will have to be developed to concentrate, and more accurately, control the differentiation of ADSC. These cells may stimulate tissues to regenerate themselves by causing or inhibiting inflammation, by emitting growth factors, or by simply touching the adjoining cells,' says Dr Lee.

Dr Wu agrees: ‘The potential of ADSC is immense; it can also be turned into gels and other cosmetic solutions. Perhaps, as cloning technology becomes more and more available and easier, we should be able to create a serum with ADSC that can be activated upon application.'

Despite its uncharted potentials and unknown risks, one thing is for sure: the future of plastic surgery and regenerative medicine is filled with fat - and that seems to be a good thing!