FIBROBLASTS 2010

UPDATE ON FACIAL REJUVENATION WITH CULTURED HUMAN FIBROBLASTS AND PLATELET-RICH PLASMA(PRP): Expert opinion by Don du Toit FRCS,PHD, Wolfson College Oxford Alumnus  and pioneer of fibroblast cell-therapy and PRP treatment in South Africa.

The application of cultured human fibroblasts to facilitate rejuvenation of the face is a cosmetic dream. All credit goes to Dr William Boss and co-workers, and Isolagen™ of the United States, that championed the cosmetic correction of soft tissue defects of the face with tiny cultured and living fibroblast injections. Dr Mentz, a plastic surgeon of Texas, United States, has pointed out that about 20 million cultured fibroblast cells per ml are needed to ensure acceptable end-point goals. This goal is seldom reached in most laboratories, due to senescence of the donor cells.
This interesting non-invasive technique of facial regeneration by fibroblast cell-therapy has been bedevilled by numerous factors. And the procedure has severe limitations, with an inability to ameliorate most of the common aging phenomenon on the face including scars, even if combined with other biologics. The most outstanding of which has been in our experience; high cost, culture failure, cell-retention failure at the recipient site with no engraftment, variable, unpredictable and short-term results, and need for numerous injections to show any result, protracted period needed before results became visible and acceptable aesthetically.  Feed-back from some cell-recipients has been poor, and they are quite right. The introduction of new fillers such as Juvederm Ultra®, and the availability of fractional laser energy for facial regeneration render superior results, putting biologics in second place. These factors, for the moment have meant the demise and non-viable commercial programs of biological skin resurfacing with autologous cultured human fibroblasts, except in a very small client cohort. The use of cultured allogeneic cells remains problematical in man, because immunological responses can be induced. Another subtle drawback is that fibroblasts harvested from some donor somatic areas, and differing embryological origins, do not engraft well in the facial dermis, which we have demonstrated in our laboratories. Not all cultured human fibroblasts are the same, and do not always engraft in the facial dermis. So the somites  and embryology of the face, also determine unavoidable outcome of engraftment of the transplanted fibroblasts, regardless of the fact that these are autologous cells and disregarded by commercial advocates of fibroblast cell-therapy as anti-aging option. What has also transpired form our biotechnology and specialist clinical experience, is that designated expanded and cultured fibroblasts, rapidly undergo senescence with poor dermal retention properties, especially in young lined-women with accelerated facial-aging due to genetic wrinkling. These are more suitable for surgical face-lift and fillers. The biological-cell associated failings, opened the door for aesthetic plasma skin-resurfacing with PRP during 2006 in Cape Town.

Platelet-rich plasma (PRP) became the next focus of aesthetic physicians regarding facial regeneration, when cultured human fibroblasts fell away. Facial regeneration and resurfacing using the clients own growth factors derived from blood-platelets. PRP as component of human blood, in South Africa, has been pioneered independently by academic doyens Callie Franz of Pretoria and Don du Toit in Cape Town. These have remained the lead laboratories with cutting edge technologies and most credible academic publications within defined protocols. Comprehensive academic studies have focused on platelet-gels, cell-biology, culture-matrices and biotechnology, tissue-culture, platelet-derived growth-factors and mechanism of action in the healing-cascade relevant to human therapeutics. During 2006, Du Toit in Cape Town demonstrated the cell-growth inducing properties of PRP in tissue culture, more specifically for fibroblasts, myoblasts, keratinocytes etc. REGENLAB/PRP/ACR®, from Mollen, Switzerland,  proved the most potent  and consistent at concentrations of 5,10, 15 and 20%. This work has confirmed by academic Japanese researchers during 2008. Aesthetic physicians have demonstrated the value of plasma-resurfacing and facial-rejuvenation by the application of PRP-mesotherapy. Results, like with cells, may be variable and inconsistent, mandating that a course of facial injections with PRP needs repeating three times a year. A new PRP product, MYCELLS®, is undergoing  testing and validation. But the comparative results of biologics have proven less effective than application of fractional facial-laser resurfacing, or chemical peeling.
The next step was the combined integration of cultured human fibroblasts and PRP as anti-aging and rejuvenation option, an ingenious concept generated in Bellville, Cape Town. Thinking behind this modus operandi, is that the PRP will provide an immediate type of biological filling effect, enhance cell-culture of human-fibroblasts ex-vivo from a skin biopsy, and the gel and growth-factors would facilitate the engraftment phase of the fibroblasts as well as cell retention. So, the approach is the use of platelet-gel, platelet-gel and fibroblast culture ex-vivo, and a combination thereof to speed up rejuvenation by the action of the platelet-derived growth factors PDGF and TGF. Provisional work from Bellville Cape Town, shows that a synergistic affect is not observed and the short-term clinical results inferior to the filler Juvederm®, especially in the nasolabial region. The introduction of the REGENLAB/ACR CELLULAR FACIAL MASK®, which provides for the topical application of PRP as rejuvenating option, ushered in a new era of facial rejuvenation during 2008. Because injections could be dispensed with, and preferred by clients, therfore bruises and ecchymosis could be avoided.

ROLE OF PRP IN AESTHETIC MEDICINE

Like facial rejuvenation with cultured fibroblasts, PRP takes a long time for visible cosmetic results to occur and clients become irritable with the slow process, compared to superficial chemical peels with exfoliation and LED photo-facial. In South Africa facial PRP-mesotherapy and ACR, was pioneered in Cape Town , by Du Toit et al. In the latter scenario the clients leave the chambers with a glowing face, especially if combined with photo-facial. However, mild-grades of hyper-pigmentation, acne and roughness do not improve dramatically, which transplanted cultured-fibroblasts  cannot achieve. Variability of skin rejuvenation results has also plagued PRP-mesotherapy in some studies and redo plasma-resurfacing is needed about two to three-times a year. The introduction of the REGENLAB CELLULAR MASK®, which rejuvenates the skin by topical application of platelet-rich plasma, without a single mesotherapy needle injection, has changed the playing fields, especially if combined with gentle MDA. See illustrations and text on this site for more details.

DEMISE OF THE CONCEPT OF TRANSPLANTED AUTOLOGOUS CULTURED HUMAN FIBROBLASTS IN THE ERA OF LIGHT THERAPY AND PHOTO-FACIALS.

The laser-light industry capitalised on the weaknesses of cultured-fibroblast facial rejuvenation. Commerce focused on stimulation of dormant and dermal resident fibroblasts by graded thermal injury or damage. By fractionated laser light accurately placed, micro-zone columns of dermal necrosis is induced. This elicits an inflammatory reaction and stimulation of resident fibroblasts to lay down collagen and renew the area. Because normal bridges are left between the thermal damaged columns, healing is so much faster, and applications so much wider than just cultured fibroblasts that have narrow options. Researchers in isolated laboratories have attempted to culture human fibroblasts in PRP and then use PRP together with cultured fibroblasts generated from the same client as a temporary biological filler and at the same time hoping to enhance biological take of the engrafted cells by the added benefit of the platelet-derived growth factors. Early open-labelled studies looking at rejuvenation end-points by this combined effort show inconsistent and disappointing results because the dynamics of PDGF and TGF are poorly understood at the moment. Manipulation of autologous human mesenchymal cells with platelet-derived growth factors in culture, changes cellular phenotype and behaviour in our experience, and in-detailed clarification in academic laboratories is needed to clarify these issues. This is important if this type of cell-PRP-gel-conglomerate is injected into a face with subtle solar damage, unstable epidermis, actinic dermatosis and potential underlying fields of growth. Very special skin assessment is needed with clinical experience in potential clients undergoing biological rejuvenation with growth factors to rule out subtle, SCC, BCC and amelanotic melanoma.
In conclusion, in the era of chemical-exfoliation and laser-resurfacing, the application of cultured autologous-human fibroblasts alone or suspended in PRP-gel constructs or matrices, since the closure of Isolagen’s® doors in London, is cost ineffective and needs more intensive research to convince the sceptics. All these biologics render temporary results, mandating maintenance treatment. Because aging affects the bones and muscles of the face, resulting in creasing and sagging, mid-face ptosis and jowls, it is understandable that biologics ( such as cultured-fibroblasts) at the moment are not the general panacea of anti-aging treatment. The introduction of the PRP-MASK® together with gentle MDA, opens a new, unexplored and exciting chapter in aesthetic medicine with the object of beauty facial restoration.

Consultant is an independent BIOMED rated-researcher, and based in Bellville, Cape Town.
Reference: D.F. du Toit et al. Biotechnological anti-aging cell-therapy treatment of facial wrinkles with cultured human fibroblasts. The Specialist Forum 2005; 5:38-46.

Posted 15 December 2008.

Disclaimer. BOLANDCELL accepts no responsibility, and readers or clients must consult a plastic surgeon and or a dermatologist for treatment options and intervention advice( both invasive and non-invasive).