BOLAND CELL FIBROBLASTS
“ISOLAGEN PROCESS” IS EFFECTIVE ADJUNCTIVE BIOLOGICAL TREATMENT FOR BEAUTY AND COSMETIC PRACTICE
The “ Isolagen Process” ( cellular rejuvenation) of autologous human fibroblast transplantation was a very useful land-mark method of facial rejuvenation/cell-based regeneration and enhanced beauty, until the company discontinued operations in 2006. It addressed the problem of facial wrinkles, tone and texture of the skin, all relevant to the aging process, by means of autologous cell biostimulation. The laboratory was based in Park Royal in London. Splendid work was done there and that London-based GMP laboratory set high, un-matcheble, benchmark standards in fibroblast cell-therapy, yet to be equalled elsewhere by other commercial cell laboratories. No other comparable cell-laboratory in the world, has to-date had the knowledge-skills, publications, expertise, specialist leadership, scientific back-up and ability to match the cell technology of Isolagen™. Few laboratories have the specialist clinical expertise that Isolagen™ had. All have failed, became non-viable, fly by night and disappeared. The cell-therapy treatment was popular as clients liked the idea of facial rejuvenation with their own cultured cells. The down-side was that it took 4-8 weeks to cultivate the client’s dermal fibroblasts that were harvested from a skin biopsy snippet taken behind the ear. Also it was labour intensive and very costly. Not all clients were happy with the skin biopsy procedure behind the ear , because it meant use of the scalpal, and occasionally went septic associated with pain. Another drawback was the problem of failed cell-culture. This has still not been rectified even by the use of tissue culture medium enrichment with A-PRP, which releases platelet-derived growth factors into the culture medium.
At the same time, Restorelle™ was a very popular substitute for the “Isolagen Process” in South Africa. Restorelle™ was the brain child of Malan de Villiers of Southern Medical, the leading biomedical laboratory based in Irene, Tswane, South Africa. The local product was very effective and cost effective compared to Isolagen™. The advantage was that the product was easy to access, and the cell purity high. There are still units using cultured human fibroblasts in South Africa to beautify the aging face.
The undisputed, doyen and specialist pioneer of autologous human fibroblast transplantation regeneration of the dermis, including specialised ex vivo tissue culture technology and use of platelet-rich plasma ( A-PRP, C-PRP) in South Africa, is Professor Donald du Toit, FRCS, of Durbanville, Cape Town. He has the first academic publications on the aesthetic, beauty and cosmetic application regarding autologous human fibroblast transplantation ( dermal regeneration by autologous cellular regeneration, or (ACR), as well as A-PRP ( also referred to as C-PRP, or just PRP) ( see references). In the anti-aging and beauty focus he has championed two autologous biological regenerative processes in cell-therapy and set unique standards: the use of platelets and fibroblasts to beautify the aging face, as well as application in the surgical clinic. This set historical benchmark standards in biological anti-aging and autologous cellular regeneratve medicine( ACR). Professor du Toit is currently specialist scientific advisor to trade and industry in South Africa and international boards, regarding the application of regenerative biologicals and formulation of clinical trial protocols. To-day the technology of ex vivo fibroblast cell expansion is a patented process in South Africa, and licensed to commercial laboratories (2006/03057). Professor du Toit has been Faculty member of the University of Stellenbosch, and a doctoral graduate of Wolfson College, University of Oxford. He presented the first South African data following autologous human fibroblast transplantation at IMCAS PARIS 2006. During 2007 he presented aesthetic data on the facial rejuvenation effects of platelet-rich plasma ( A-PRP or C-PRP) at IMCAS 2007 Bangkok. He was teaching faculty of IMCAS PARIS 2008 and gave a dissertation on the scientific basis and proof-of–science of platelet-rich plasma (PRP), based on advanced digital imaging and skin-relief ( skin-analysis) in cosmetic medicine and facial rejuvenation. The application of the mesogun and PRP was demonstrated to a packed workshop. Similar presentations were made at the Aesthetic Medicine Congress held at Galagher Estate, Gauteng. During 2008 further data will be presented on the 3-year follow-up and advanced skin quantification analysis after autologous fibroblast transplantation (AFT) for facial wrinkling ( fibroblast cell therapy). Professor du Toit, has pointed out important cell morphological, tissue culture and flow cytometric quantification facts, based on research in his photo-light laboratory regarding cell therapy for facial rejuvenation:
- The “Isolagen Process” is more effective than the use of RF, IPL and fractional ( including mosaic) photo-thermolysis as anti-aging option, but invariable and no-results sometimes do occur. These are attributed to translational errors in cultivated senescent fibroblasts that inhibit collagen release, in some patients.
- Tissue culture of human fibroblasts ex vivo can be enhanced by A-PRP in co-culture that provides for 3D cell proliferation that differs from 2D monolayer planar proliferation. This is patented technology by PTC registration 2008 ( PTC/EP 2007/058695). PRP mesotherapy given concomitantly with fibroblasts has a slight additive effect, but is modest and subtle. Cosmetic creams such as Neostrata® Renewal cream ( 12 PHA) and Neostrata® High Potency Cream ( Lactobionic formulation:20 AHA) are strongly recommended after AFT and A-PRP facial mesotherapy, together with face sunscreens. M-Activ is a good alternative cosmetic cream. The rejuvenation process can be enhanced by the action of 633nm LED light phototherapy. REGENLAB® PRP, and REGENLAB-KIT® is distributed by Omnimed ( PTY)., Ltd., Randburg, South Africa.
- A-PRP facial mesotherapy alone has advantages over autologous human fibroblast transplantation, and is a more rapid process because tissue-culture in a laboratory is not needed. However the two forms of rejuvenation differ because A-PRP relies on the GF released by platelet-gel and autologous fibroblast transplantation deposits collagen. A-PRP can be done in a doctor’s practice without need for laboratory culture facilities and services. Larger areas of the face can be rejuvenated at one sitting by PRP mesotherapy, than during the fibroblast cell therapy approach. AFT needs a minimum of three fibroblast injections or vials. So two different actions of rejuvenation: the one by GF release from activated platelet-gel and the other deposition of collagen by the engrafted fibroblasts into the dermis and a paracrine effect. In the first, a platelet-gel is used, and in the latter, cultured fibroblasts. Trials have demonstrated these effects that have been quantified by advanced skin-analysis and reported. A-PRP is as effective as fractional laser treatment, is far cheaper but needs to be repeated 6 monthly in some clients. Botulinum is the most effective rejuvenation option in young woman.
- Ongoing clinical trials assessing rejuvenation-index, skin analysis and cosmetic creams regarding A-PRP and autologous human fibroblast transplantation, alone and in combination, with new culture technology is been conducted in three centers, as of 2007. RF, IPL and laser is used as adjuvant therapy. Results look promising and the first presentation on the use of AHF will be presented during the latter half of 2008 at an aesthetic congress.
Figure 1: Biotechnology for skin and cosmetic rejuvenation. Dermal human fibroblast tissue engineering technology ex vivo monolayer culture with A- and C-PRP driven mediums ( PTC patent: PTC/EP2007/058695: patent 2006/030357).
REFERENCES: RELEVANT TO AUTOLOGOUS HUMAN FIBROBLAST CELL THERAPY AND PLATELET RICH-PLASMA ( 2007-2008).
- Du Toit DF et al. Biotechnology. Cultured human fibroblasts. The Specialist Forum. 5:38-46, 2005.
- Du Toit DF et al. Link between the human fibroblast, connective tissue disorders and shoulder. International Journal of Shoulder Surgery.1:87-95,2007
- Du Toit DF et al. Tissue-culture dynamics, regeneration and molecular biology perspective. International J of Shoulder Surgery. 1: 52-61,2007
- Du Toit DF et al. Platelet-rich plasma: the clinical potential of autologous corneal keratinocyte replacement technology for corneal blindness in South Africa. 2007
- Du Toit DF et al. Platelet-rich plasma: simultaneous co-culture of fibroblasts ex vivo in 2D and 3D media allows assessment of different phenotypes, using REGENLAB™ Technology. 2007
- Du Toit DF et al. Platelet rich plasma induced cell locomotion in TC. Can fibroblast cell crawling occur from 3D to 2D media? 2007
- Du Toit DF et al. Platelet-rich plasma: dermal–epidermal junction dynamics of keratinocytes and fibroblasts during tissue culture. 2007
- Du Toit DF et al. Platelet-rich plasma and wound healing. Fibroblast proliferation dynamics monitored in ex vivo tissue culture. 2008
- Du Toit DF et al. Platelet-rich plasma. Enhanced fibroblast and keratinocyte membrane ruffling and signal transduction. 2007
- Du Toit DF et al. Platelet rich plasma. Fibroblast and keratinocyte cell shape and morphology differ in cytokine driven 3D matrices and 2D coated TC surfaces.2007
- Du Toit DF et al. Platelet-rich plasma. 3D TC dendritic-induced cell plasticity and facial arterial converging points. An hypothesis for enhanced skin tumour pathogenesis.2007
The relevance of cultured human dermal fibroblasts is explained. Knowledge of the basic sciences of the fibroblasts is of critical importance in understanding application of laser, radiofrequency therapy and IPL rejuvenation of the solar-aged face. Many modalities and beauty treatment options exist for the management and amelioration of facial wrinkles. Rejuvenation may be accomplished by the judicious application of laser light, IPL, Botox, vitamin-A containing creams, fillers, surgical face-lifts, to mention a few. Most afford temporary results and intermittent ongoing treatment is needed, especially in the case with the use of Botox. Poor results can be anticipated if the person does not address diet, regulation of the menopause, does not avoid further solar damage, persists to abuse alcohol, ignores the correct use of moisturizing face creams and continues to smoke cigarettes, if these adverse factors are not removed then facial rejuvenation will fail and wrinkles will increase. A deeply lined face can be expected with a leathery complexion. The supplementation of the diet with cell foods, proteins and collagen are of unproven value in the restoration of skin elasticity. Modest supplementation of the diet with vitamins is of value. The place of herbs remains questionable.
Facial regeneration and rejuvenation may also be achieved by the use of the patient's own body cultured cells, termed human fibroblasts (youth cultivated in a test tube). These cells are found in the dermis of the human skin, release collagen, and is thought that dysfunctional fibroblasts are associated with the aging process of the skin and wrinkle formation. These cells have now been shown to play a key role in the aging process, cytoskeleton of the skin dermis, and are responsible for key components of wound healing. There is a key interaction between human dermal fibroblasts and the surrounding extracellular matrix ( ECM). Facial rejuvenation and wrinkle amelioration is now also possible by injecting the patient's own cultured dermal fibroblasts, obtained from a skin biopsy, underneath and adjacent to ugly facial wrinkle lines around the eyes and mouth. With time the transplanted cells produce collagen strands that can ameliorate wrinkles. Usually three to four injection appointments are needed in the doctors' rooms at one to two weekly intervals. This is not filler therapy but, is a more natural protein process to ameliorate wrinkles by using the patient's own cells. The treatment was introduced into clinical practice during 2000 and several thousand persons have received fibroblast therapy for wrinkle restoration. This is appealing to many persons because artificial fillers can be avoided. Because it is a biological treatment the restoration process is slow and can take months. In many patients, results can persist for months if not years, which is not achievable with Botox (that needs repeated injections to keep the face smooth). Briefly, the human cultured fibroblast process is as follows. The facial wrinkles are defined that need amelioration. After informed consent is given, a small skin biopsy is obtained under local anaesthesia in a doctors consulting room or hospital theatre. The skin is sent to a laboratory where the persons fibroblasts are cultured and expanded over a 4- 6 week period. The cultured fibroblasts are then injected underneath the defined wrinkles. This process is generally pain free after application of topical anaesthetic agent a half hour before injection. Multiple small injections are done at each sitting, and the process is safe. Occasionally persons complain of local redness and swelling but in all cases this subsides in a few hours. In some patients very positive changes in skin texture are visible within 14 days. Regeneration is an ongoing process and results are reported as long as 5 years after commencement of treatment. Glabellar, nasolabial, and crow feet wrinkles can be eradicated by cell therapy. Very positive results are obtained with the use of cells and judicious application of vitamin-a based creams. Skin improvement can be monitored by the application of skin collagen ultrasound. The treatment is available in Cape Town and the total cost, including doctors consultations is below R5000. This is affordable for both men and women on a tight budget. In Europe and the United States the process is very expensive and varies from R40000 to 50000.
BOLAND CELL : SCIENTIFIC AND ACADEMIC DISCUSSION ( FIBROBLASTS).
Facial rejuvenation technology and anti-aging methods to turn back the clock and reverse wrinkles on the face can be found in most lay publications. Sadly the three constants in life are taxes, wrinkles and death. Methods to improve the photo aged face include, correct nutrition, optimal management of the menopause, avoidance of the damaging rays of the sun, wearing sun protectants, collagen, creams and possibly Botox. Facial skin tightening by the use of IPL has also become popular and supposedly works by enhancement or stimulation of dermal fibroblasts. Another way is to manage facial wrinkles by the biological route. The patented process described by IsolagenT is well documented. It is safe therapy because the patient's own cells are used. Fairly good results have been reported, especially if used with effective creams. The process of using cultured dermal fibroblasts dates back to 2000. It is not a filler and can be used in-conjunction with RestalyneT, Botox and IPL. Long lasting results have been reported in excess of 5 years. It is popular treatment and patients like the approach. Sadly, the biological approach has been threatened by the advent of and application of IPL and radiofrequency in beauty salons to rejuvenate the face. See resources: Du TOIT et al. The Specialist Forum 5: June 2005 38-46 ( South African Publication), Clinics in Plastic Surgery 27: 613-626, 2000; Ann Plast Surg 44, 536-542, 2000, Junqueira et al. Text and Atlas, Lange, New York, 2003: 369-379).
POSTED AND UPDATED: 30 May 2008