Autologous fibroblasts in the fight against skin aging processes

Vladimir Tsepkolenko, Honored Doctor of Ukraine, Doctor of Medical Sciences, Professor of the Department of Dermatovenereology of the National Medical Academy of Postgraduate Education named after. P. L. Shupika, Institute of Plastic Surgery (Ukraine)

Anna Tsepkolenko, head. Department of Regenerative, Laser and Phototechnologies of the Virtus Clinic, dermatovenerologist, specialist in laser technologies (Ukraine)

In the field of aesthetic medicine, regenerative technologies have opened the way to effective and safe restoration of the full structure of the skin, including the correction of age-related changes.

In particular, rejuvenation using autologous dermal fibroblasts is of wide interest to researchers and practitioners.

In 1999, the United States published materials from a large-scale clinical study conducted in 1995⎼1999, in which 1,450 patients with severe facial wrinkles took part. Its results proved both the effectiveness of the rejuvenation method using autofibroblasts (follow-up period was 24⎼48 months) and its safety. A clinical effect was obtained in the form of a reduction in the number and depth of wrinkles, and the absence of complications was recorded. Multicenter placebo-controlled studies from 2003 to 2008 (involving 800 patients followed for 12 months) showed a statistically significant reduction in wrinkle depth after the use of autofibroblasts. The obtained result was maintained throughout the observation period. However, despite the obvious effectiveness of the presented method, the use of autofibroblasts in cosmetology practice is significantly limited by the need to introduce them in large quantities to achieve a pronounced clinical effect.

It is known that the telomere length of human skin fibroblasts decreases by approximately 150 bases with each cell division, limiting the number of cell divisions, which average 50 + 10 ( Gawthon RM, 2002; Ramkumar Menon, Jie Yu et al., 2014 ). The same thing happens in fibroblast culture.

Special studies have been carried out, which include checking telomere length and gene activity, and epigenetic mechanisms for cultivating autofibroblasts have been developed, which made it possible to obtain their active forms for use in practical medicine. This made it possible to reduce the dosage of cellular biomaterial.

We have developed and patented (patent No. 95130 dated December 10, 2014) a new algorithm for the complex correction of involution-dystrophic skin changes using fibroblasts - a procedure called neofibrolifting .

Algorithms for neofibrolifting

The procedure consists of two or three consecutive stages based on the impact on key points of skin aging , such as:

• reduction of skin water resources;

• changes in the three-dimensional organization of the skin associated with a decrease in the level of collagen, elastin and reticulin in the dermis;

• violation of blood microcirculation in the skin;

• a decrease in the number of fibroblasts and a weakening of their biosynthetic activity as a result of a decrease in microcirculation and the volume of incoming nutrients.

The number of stages and their features depend on the severity of involutional changes in the skin.

With pronounced age-related skin changes

First stage. The following steps are carried out sequentially:

• ultrasound examination to assess the condition of the skin, its thickness and structural elements;

• Ultrasound Doppler scanning of the skin to determine the speed of blood circulation;

• selection of a small piece (biopsy) of skin for cultivating the required number of dermal autofibroblasts in a biotechnological laboratory;

• injections using the mesotherapy method of autologous plasma enriched with growth factors to stimulate revascularization and create the most favorable conditions for the engraftment and functioning of fibroblasts.

The first stage procedures are carried out on the same day, without an interval between skin sampling and PRP injection.

Second phase. Repeated PRP therapy procedure two weeks later.

The third stage is carried out after another two weeks ⎼ this interval is necessary to obtain the effect of revascularization after the introduction of PRP and skin regeneration after laser exposure. By this time, the process of cell cultivation is completed ⎼ four weeks from the moment of taking the skin biopsy.

The following are executed sequentially:

• for the purpose of control ⎼ repeated ultrasound examination of the skin and study of its blood circulation parameters;

• introduction of dermal autofibroblasts in an amount from 14 to 30 million cells, depending on the severity of age-related skin changes.

Fourth stage . Maintaining the result by stimulating the injected autologous fibroblasts using the procedure of ablative fractional photothermolysis or other hardware methods of influencing the skin (RF-lifting, IPL, DOT, etc.) in order to reduce the collagen formed as a result of the action of the injected dermal autofibroblasts.

The result of the course is an improvement in the appearance of aging skin and an improvement in the patient’s quality of life.

With moderate severity of age-related skin changes

The first stage is the same as for patients with significant age-related skin changes.

The second stage is similar to the third stage, which is assumed for pronounced age-related changes in the skin. It is carried out 4 weeks after the first one (the time required for culturing dermal autofibroblasts).

Clinical results

A study was conducted on 157 patients aged 36 to 57 years. Reason for visiting the clinic ⎼ signs of aging facial skin: fine wrinkles in the forehead, in the periorbital area, nasolabial folds, decreased skin turgor, unclear facial contour.

The patients were divided into two groups: the first (30 patients ⎼ control group) received traditional cosmetic care, the second ⎼ treatment using the neofibrolifting system.

Before and after treatment, each patient was prescribed a number of studies :

• photo documentation;

• digital dermatoscopy;

• corneometry (determination of skin moisture);

• determination of transepidermal water loss.

The results of the study showed a pronounced positive dynamics of the skin condition in patients treated with the neofibrolifting system, according to such basic indicators as acoustic density indicators improved by 15⎼20%, and volumetric blood flow rates by 15⎼20%.

The use of the neofibrolifting method makes it possible to achieve a high level of correction of skin conditions with age-related changes of varying degrees of severity.

Contraindications:

• acute and chronic skin diseases;

• blood clotting disorder;

• tendency to form hypertrophic and keloid scars .

After treatment, no special rehabilitation is required; injection marks disappear within three days, as after conventional mesotherapy. The positive effect of the procedure increases over time; the final result can be assessed in a month.

The criteria for the quality of treatment are the disappearance or reduction of wrinkles, improvement of the functional state of the skin, improvement of the psycho-vegetative state, and improvement of quality of life indicators.

If the proposed treatment protocol and sanitary and epidemiological standards were followed, no side effects or complications were identified.

First published in Les Nouvelles Esthetiques 2017/№5