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Biorevitalization and cosmetic surgery of the face: Synergies of action
Abstract
Polydeoxyribonucleotide (PDRN) is used in aesthetic medicine as a skin revitalyzing agent as well as to correct depressed scars and striae distansae. The purpose of this study is to evaluate the effect of PDRN in stimulating skin biorevitalization of the face in women who underwent to a complete face-lift or a mini lifting procedure, not only to improve the cosmetic appearance but also to create more suitable conditions to better tolerate surgery. 15 female patients with an age ranging from 28 and 58 years (mean age 46) who had to undergo to a mini lifting procedure (10 patients) and a complete face-lift (5 patients) were treated in four sessions preoperatively, once a week, with intradermal administration of PDRN. Four more sessions, again on a weekly basis, were carried out starting from day 15 post-operatively. During the week before surgery and the two weeks following it, a home therapy consisting of one i.m. PDRN vial a day was offered to the patients. In all treated patients scar healing was normal, with no evidence of diastase and/or delayed scarring. Morevover the skin showed a good eutrophication and the suture stitches were removed a few days earlier than in the case of the traditional protocol (on day 10 instead of day 12). The patients' subjective evaluation was positive in all cases and extremely positive in 35% of them. The results of the study reveal a trophic and revitalizing action of PDRN on the skin which is therefore useful to improve the cosmetic appearance of the face and to create those conditions that assure a better tolerability of the stress due to surgery, and to reduce the healing time.
... At the first treatment session, all subjects received PN-HPT ® coformulated with hyaluronic acid intradermally to maximize the immediate volume-enhancing effect and prime the dermal fibroblasts to full PN-HPT ® activation over the following treatment sessions. 9,10 Using specifically designed, low-concentration, single-agent PN-HPT ® formulations in delicate areas such as eyelids and the periocular district minimized the incidence of wheals occasionally occurring with more concentrated PN-HPT ® formulations with or without hyaluronic acid. 9,11 The unique low-dose PN-HPT ® formulations used in such delicate areas were Plinest ® fast (7.5 mg/ml of PN-HPT ® in 2-ml prefilled syringes) and Plinest ® Eye (7.5 mg/ml of PN-HPT ® intradermic gel designed explicitly for eye contour in 2-ml prefilled syringes). ...
... 9,10 Using specifically designed, low-concentration, single-agent PN-HPT ® formulations in delicate areas such as eyelids and the periocular district minimized the incidence of wheals occasionally occurring with more concentrated PN-HPT ® formulations with or without hyaluronic acid. 9,11 The unique low-dose PN-HPT ® formulations used in such delicate areas were Plinest ® fast (7.5 mg/ml of PN-HPT ® in 2-ml prefilled syringes) and Plinest ® Eye (7.5 mg/ml of PN-HPT ® intradermic gel designed explicitly for eye contour in 2-ml prefilled syringes). ...
Background
Wasting of soft tissues leads to flattening and deflation of the aging midface skin. Polynucleotides Highly Purified Technology (PN-HPT®) demonstrated dermal hydration and elasticity as well as fibroblasts vitality and activity.
Aims
To probe the value of PN-HPT® in middle third rejuvenation in an open-design, exploratory prospective cohort study in 40 real-life ambulatorily treated women.
Methods
Three treatment sessions—at baseline (2-ml prefilled syringe containing 10 mg/ml PN-HPT®, 10 mg/ml hyaluronic acid, 200 mM mannitol) as intradermic gel, and after 3 weeks (2-ml prefilled syringe containing 20 mg/ml PN-HPT® intradermic gel) and 6 weeks (same treatment as baseline). The protocol allowed supplemental treatment with specifically formulated PN-HPT® (7.5 mg/ml) when needed in periocular and eyelid areas. Assessments: sequential photographs of the facial middle third at baseline, third treatment session and 6–8 weeks after the third treatment session; scoring of overall skin quality and texture, skin quality determinants (wrinkles and skin roughness, skin elasticity, skin brightness), scar appearance, and subjective satisfaction with impromptu 10-cm Visual Analogue Scales.
Results
Significant improvement of overall skin quality and texture (from 7.0 ± 1.06 at baseline session to 7.8 ± 0.99 at follow-up), associated with highly significant improvements of wrinkles and skin roughness, elasticity, and brightness (–17.1%, +39.6%, and +51.1%, respectively). The severity scores of post-acne scars decreased from 7.6 ± 1.32 to 4.2 ± 2.13. Individual satisfaction score at the end of treatment: 0.8 ± 0.28.
Conclusions
PN-HPT® candidate as a valuable option for facial middle third rejuvenation. Further trials will hopefully confirm these early results.
... The pre-and post-operative adjuvant treatment improved surgery outcomes and reduced further tissue scarring, softened contracted nasal skin; greater mobility was also observed. Cavallini [140] treated 15 female patients (mean age 46) with intradermal administration of PDRN in four sessions before and after a complete face-lift or a mini lifting procedure. Furthermore, the patients received one intramuscular injection of PDRN a day the week before surgery and 2 weeks after it. ...
Aim: The present study evaluated the effects of polydeoxyribonucleotide (PDRN) on tissue regeneration, paying special attention to the molecular mechanisms that underlie its tissue remodeling actions to better identify its effective therapeutic potential in wound healing. Materials & methods: Strategic searches were conducted through MEDLINE/PubMed, Google Scholar, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials, from their earliest available dates to March 2020. The studies were included with the following eligibility criteria: studies evaluating tissue regeneration, and being an in vitro, in vivo and clinical study. Results: Out of more than 90 articles, 34 fulfilled the eligibility criteria. All data obtained proved the ability of PDRN in promoting a physiological tissue repair through salvage pathway and adenosine A2A receptor activation. Conclusion: Up to date PDRN has proved promising results in term of wound regeneration, healing time and absence of side effects.
... Newly deposited and produced collagen matrix on dentin particles was observed used for healing of cuts and skin regeneration and was composed of parts of low molecular DNA. As purine and pyrimidine nucleotides are formed as a polymer of deoxyribonucleotides which are composed of 50~2000 bases with a combined form via phosphodiester combination, they supply purine and pyrimidine as well as deoxyribonucleotides and deoxyribonucleosides [11]. It is reported that as for PDRN, nucleotides and ne growth of various shapes of cells, synthesis of nucleic acid and healing of cuts [12,13], salvage pathways to create nucleic acid with low energy consumption [14,15], and activate A2 purinergic receptors [16]. ...
This study examined the osteoinductive activity of demineralized dentin matrix (DDM) from human and polydeoxyribonucleotide (PDRN) for nude mice.
Twenty healthy nude mice, weighing about 15~20 g, were used for the study. DDM from human and PDRN were prepared and implanted subcutaneously into the dorsal portion of the nude mice. The nude mice were sacrificed at 1, 2, and 4 weeks after grafting and evaluated histologically by hematoxylin-eosin and Masson’s trichrome staining. The specimens were also evaluated via a histomorphometric study.
The DDM and PDRN induced new bone, osteoblasts, and fibroblasts in soft tissues. The histological findings showed bone-forming cells like osteoblasts and fibroblasts at 1, 2, and 4 weeks. New bone formation was observed in the histomorphometric study. In particular, the ratio of new bone formation was the highest at 2 weeks compared with the first week and fourth week.
In this study, we showed that the PDRN used in this experimental model was able to induce bone regeneration when combined to the DDM.
... In recent years, new filler products made from purified polynucleotides (PNs) derived from the germ cells of salmon and other fish have been developed and are now being used in Europe. It has been reported that, while existing filler products simply fill the contracted or depressed space, the PN-containing products not only fill the space, but improve tissue regeneration in the environment of damaged tissue, resulting in more natural tissue regeneration (1). ...
Aging well has become the new target of preventative medicine, and aesthetic dermatology can contribute to this request. The polynucleotide (PN) containing products not only fill the space, but improve tissue regeneration, resulting in more natural tissue regeneration. Five Korean women received four times injections of long-chain PN filler in two-week intervals for skin rejuvenation. About 0.05 mL of material was injected in 40 points of one-side cheek. The pore and skin thickness were markedly improved in the patients in their 30s, whereas skin tone, melanin, wrinkles, and sagging were noticeably improved for patients in their 40s. There are no serious side effects. In conclusion, intradermal long-chain PN filler injection seems to be an effective and safe treatment for skin rejuvenation.
... In recent years, these new filler products, made from purified polynucleotides derived from germ cells of salmon and other fishes, have been used in central Europe. While previously existing filler products simply fill a contracted or depressed space, the polynucleotide-containing products not only fill the space, but also improve the regeneration environment of damaged tissue, resulting in more natural tissue regeneration (5). It has been reported that polynucleotides promote the growth of human corneal fibroblasts and increase reparation on ultraviolet B (UVB)-damaged dermal fibroblasts (3). ...
The Rejuran® is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran® on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire®; and Group 3 were treated with Rejuran®. The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran® treatment for crow's feet on one side and Yvoire-Hydro® on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran® group showed similar durability and inflammatory response to the Yvoire® group. Upon efficacy assessment, the Rejuran® group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran®, as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.
Graphical Abstract
Background:
No data on the clinical results and safety profiles of the polycaprolactone (PCL) -based dermal filler for crow's feet correction have been published.
Aims:
This study was designed to compare the efficacy and safety of a novel PCL-based dermal filler, DLMR01, with that of RJR, a purified polynucleotide dermal filler.
Patients/methods:
A total of 30 subjects with symmetric crow's feet of 2-4 points on the Crow's Feet Grading Scale (CFGS) were enrolled in this randomized, patient/evaluator-blinded, split-face study. Each subject was randomized to receive injections of DLMR01 or RJR in their right or left crow's feet. At 4 and 12 weeks, all participants were evaluated via CFGS, Global Aesthetic Improvement Scale (GAIS), and PRIMOS software system.
Results:
No significant difference in CFGS, GAIS, and Ra value was detected between DLMR01 side and RJR at 12 weeks (improvement rate in CFGS from baseline at week 12-DLMR01: 48.28% [14/29], RJR: 41.38% [12/29]).
Conclusion:
The novel PCL-based dermal filler DLMR01 shows suitable efficacy and safety, widening the selection possibilities for clinicians and patients in the treatment crow's feet.
Biorejuvenation is a common term to indicate mesotherapy for skin rejuvenation (also called biorevitalization or mesolift). It’s a technique used to rejuvenate and tone the skin by means of an injection in the superficial dermis of suitable products, perfectly biocompatible and totally absorbable.
The goal of this technique is to increase the biosynthetic capacity of fibroblasts, inducing the reconstruction of an optimal physiologic environment, facilitating interaction between cells, and increasing collagen, elastin, and hyaluronic acid (HA) production [1, 2].
The desired final effect is a firm, bright, and moisturized skin. A
Nowadays dermatological aesthetic treatments requires the use of well tolerated, tested, low invasive procedures, allowing the patients a prompt return to normal social life. This is why skin biorevitalization is a very frequent treatment, also because it can be used as an antiaging therapy by itself, as well as to prepare the skin for other aesthetic procedures. Authors describe the clinical experience on skin biorevitalization with long chain polynucleotide gel (Plinest®) for intradermal infiltration - a class III medical device, biocompatible, natural, entirely resorbable and not requiring allergy test. 143 patients of both sexes were submitted to 3 or 4 sessions of intradermal infiltration with the product in study according to the type of skin. The evaluations were performed before and 30 days after the last treatment. Results: The physician global assessment was positive in 91% of the cases, with a clinical improvement due to the reduction of superficial tine wrinkles and to a best appearance of the skin mainly pronounced in the cheeks, in the periocular area and in the neck. A digital skin measurement system for hydration, sebometry, pH and elasticity was performed in 14 patients. Data showed increase in hydration, and improvement of elasticity (21,8%). The product was very well tolerated and the injections did not cause much pain. There were no cases of severe side effects due to the product used in the study. The data obtained till now are in accord with the action of stimulous of secretion of collagenic and non collagenic proteins by fibroblasts, due to the activity of long polynucleotides molecules, but a greater number of cases are suitable to confirm these clinical results.
Mesotherapy is widely utilized in Europe for skin rejuvenation. © 2012 Springer-Verlag Berlin Heidelberg. All rights are reserved.
Mesotherapy is a method of treatment in which small doses of drugs or other biologically active substances are injected into lesions intra and subcutaneously. Mesotherapy was first used in 1952 by the French doctor M. Pistor. Currently this method is widely popular, particularly in aesthetic dermatology. It is a noninvasive procedure, which without surgical intervention produces satisfactory therapeutic results. Mesotherapy may play a role in the treatment of hair disorders, symptoms of skin ageing, scars, keloids, stretches and cellulitis. Intracutaneous injections of biologically active substances increase cell metabolism and stimulate fibroblasts to produce collagen and elastin, influencing microcirculation in the dermis and subcutaneous tissue. Injections of hyaluronic acid cause immediate skin rejuvenation and long-term stimulation of collagen and elastin. Mesotherapy accelerates the process of wound healing, and is used.
La biostimolazione cutanea è un terapia distrettuale atta a stimolare i fibroblasti a produrre elastina, collagenee, acido ialuronico; a favorire un incremento numerico di tali cellule insieme a un loro riequilibrio metabolico, a rallentare il metabolismo catabolico del collagene (inibendo proteasi e collagenasi), dell’acido ialuronico (inibendo le ialuronidasi), dell’elastina (inibendo le elastasi) e a realizzare un’azione scavenger dei radicali liberi dell’ossigeno. Viene effettuata in particolare nelle zone fotoesposte (viso, collo, decolleté, mani) con lo scopo di rallentare l’invecchiamento cutaneo, di assicurare alla pelle una buona luminosità, una buona elasticità, un buon turgore. Per realizzare una biostimolazione cutanea vengono utilizzati diversi principi attivi quali: la glucosamina solfato, aminozucchero naturalmente presente nell’organismo sotto forma di glucosamina-6-fosfato; il polidessossiribonucleotide, miscela di frazioni di DNA a basso peso molecolare, ottenute da pesce destinato all’alimentazione umana; l’acido ialuronico, carboidrato complesso appartenente alla famiglia dei glucosaminoglicani (GAG), che viene utilizzato a questo scopo in una composizione a basso peso molecolare (600 000/1 000 000 Dalton) non cross-linked, concepito per essere riassorbito in tempi brevi. Di recente, viene inoltre utilizzata una metodica fisica di biostimolazione cutanea (fotobiomodulazione) che consiste in una tecnica di stimolazione cellulare attuata tramite una luce emessa da una sorgente laser a diodi che non emette calore (Light Emitting Diode). L’emissione di luce LED è un approccio essenzialmente nuovo per contrastare il photoaging e si basa sull’emissione di basse quantità di energia atta a ripristinare il collagene.
The aim of mesotherapy for skin rejuvenation is to increase the biosynthetic capacity of fibroblasts, inducing the reconstruction of an optimal physiologic environment, the enhancement of cell activity, and the synthesis of collagen, elastin, and hyaluronic acid. The desired final effect is a firm, bright, and moisturized skin, and the injection in the superficial dermis of suitable products--perfectly biocompatible and totally absorbable--can achieve these results. In addition to a daily sunscreen application and nonsmoking, mesotherapy is another antiaging strategy helping to maintain a globally firm and bright skin, protecting it from the environmental contributors to aging.
Factors controlling relative flux rates of the de novo and salvage pathways of purine nucleotide biosynthesis during animal cell growth are not fully understood. To examine the relative role of each pathway for cell growth, three cell lines including CHO K1 (a wild-type Chinese hamster ovary fibroblast cell line), CHO ade -A (an auxotrophic cell line deficient of amidophosphoribosyltransferase (ATase), a presumed rate-limiting enzyme of the de novo pathway), and CHO ade -A transfected with human ATase cDNA (-A+hATase) resulting in 30-350% of the ATase activity of CHO K1, were cultured in purine-rich or purine-free media. Based on the enzyme activities of ATase and hypoxanthine phosphoribosyltransferase, the metabolic rate of the de novo and salvage pathways, the rate of cell growth (growth rate) in three cell lines under various culture conditions, and the effect of hypoxanthine infusion on the metabolic rate of the de novo pathway in rat liver, we concluded the following. 1) In -A+hATase transfectants, ATase activity limits the rate of the de novo pathway, which is closely linked with the growth rate. 2) Purine nucleotides are synthesized preferentially by the salvage pathway as long as hypoxanthine, the most essential source of purine salvage, can be utilized, which was confirmed in rat liver in vivo by hypoxanthine infusion. The preferential usage of the salvage pathway results in sparing the energy expenditure required for de novo synthesis. 3) The regulatory capacity of the de novo pathway (about 200%) was larger than that of the salvage pathway (about 20%) with constant hypoxanthine phosphoribosyltransferase activity.
The effect of polydeoxyribonucleotide (PDRN) vs. placebo on the wound healing process in patients undergoing skin grafts during reconstructive surgery was evaluated. In this double-blind, placebo-controlled study, 58 patients of both sexes subjected to skin grafts were studied and randomly allocated in two homogeneous groups treated with standard therapy plus PDRN (3mL ampoule contains PDRN mg. 5.625) or placebo. PDRN or placebo were administered by intramuscular injection once daily for 10 days and by perilesional infiltration at Days 1 and 5, postoperatively. Checks were carried out at the end of surgery and after 5, 10, 14, and 21 days. The primary end point of the trial was the rate of repair of the graft donor site. At the beginning, the two groups were homogeneous in terms of age, sex, and size of the graft donor site. On Day 10, the surface of the reepithelized area was 26.7±6.2cm2 (mean± SD) in the PDRN group and 20.7±6.7cm2 in the placebo group (p<0.01 between groups). On Day 14, the graft donor site was completely reepithelized in 17 out of 29 (58.6%) patients treated with PDRN and in 5 out of 29 (17.2%) patients treated with placebo (p<0.01 between groups). At the end of the trial, all graft donor sites appeared to be clinically healed. The data of the trial show the stimulation action of PDRN on tissue repair processes, with no significant side-effects. A more regular regression of pain symptoms was also observed in the PDRN group (p<0.01 between groups on Days 10 and 14).
Extracellular purine nucleosides and nucleotides in micromolar concentrations stimulate proliferation of a variety of cell types in vitro and in vivo. As well they act synergistically with NGF to stimulate neurite outgrowth from PC12 cells. A variety of purine nucleosides and deoxyribonucleosides promote cell proliferation and increase intracellular cAMP. Their activities are inhibited by adenosine A2 receptor antagonists. Only adenosine interacts with the A2 receptor. We propose that the other nucleosides and deoxyribonucleosides inhibit extracellular adenosine deaminase, thereby increasing the extracellular concentration of adenosine. The nucleotides apparently act by stimulating P2y receptors coupled to inositol phosphate metabolism. We propose that the nucleosides and nucleotides act synergistically with other growth factors because each has distinct but complementary second messenger systems. If our hypotheses are correct, it should prove possible to modulate the growth and morphogenesis in several cell types using drugs that inhibit or stimulate adenosine A2 or purine P2y receptor agonists or the second messenger systems coupled to these receptors.
The present studies were done to determine the effect of selected adenine nucleotides on healing of wounds made by mechanically denuding areas in confluent monolayers of renal tubular epithelial cells. We found that hydrolyzable and nonhydrolyzable forms of ATP but not UTP stimulated healing of LLC-PK1 cell wounds, while both ATP and UTP promoted healing of MDCK cell wounds, suggesting that different subtypes of purinoceptors regulated wound healing in these cells. Stimulation of wound healing by ATP was equivalent in control cells and in cells in which irradiation suppressed proliferation, suggesting a prominent role for cell migration in the healing process. Since ATP receptors are often linked to activation of protein kinase C, the effect of a protein kinase C activator (4 beta-phorbol 12-myristate 13-acetate, PMA) on wound healing was studied. Long-term (24 hr) exposure to PMA inhibited while short-term (30-120 min) exposure to PMA enhanced cell wound healing. Two chemically and mechanistically dissimilar protein kinase C inhibitors (calphostin C and chelerythrine) inhibited LLC-PK1 and MDCK cell wound healing, and calphostin C prevented ATP enhancement of LLC-PK1 healing. These observations suggest a role for protein kinase C in regulation of basal and adenine nucleotide-stimulated wound healing. Adenosine triphosphate did not affect cell-cell adhesion of either LLC-PK1 or MDCK cells. Adenine nucleotides and PMA enhanced and calphostin C inhibited short-term adhesion of LLC-PK1 and MDCK cells to plastic and to other substrates such as fibronectin, laminin and collagen type IV.(ABSTRACT TRUNCATED AT 250 WORDS)
A simple assay capable of evaluating the trophic effect of growth factors or active principles on human skin diploid fibroblasts in primary culture has been developed. The results indicate that at physiological concentrations (20-100 micrograms/ml) a human placental polydeoxyribonucleotide (PDRN) preparation enhances the growth of human skin diploid fibroblasts of the knee in primary culture. This effect is consistently reproducible in the case of patients over 60 years of age, and may explain previously reported data on the successful clinical applications of human placental preparations, suggesting a selective benefit of PDRN in wound healing when compared to other treatments.
We previously showed that intravenous total parenteral nutrition supplemented with nucleosides and nucleotides (NS/NT) promoted ulcer healing in rats with indomethacin-induced ileitis. The present study evaluated whether dietary NT supplementation would similarly affect ulcer healing in this model. Female Lewis rats were randomized into either control or experimental groups receiving yeast RNA containing NT or arginine, glutamine, fish oil, guar gum, or a combination of yeast RNA+arginine diets. Ileitis was induced by two doses of indomethacin (7.5 mg/kg) administered subcutaneously 24 hr apart. Ulcer number and length were determined at 4, 8, and 14 days after induction of ileitis. Ileal villous and crypt length, crypt-villous ratio, and bromodeoxyuridine (BrdU) labeling were studied in the control and yeast RNA-supplemented diet groups. Ileal ulceration was present in all groups at 4 and 8 days and was almost healed by 14 days. Rats receiving yeast RNA, arginine, and yeast RNA + arginine diets showed a significant decrease in ulcer number (56%, 28%, and 34%, respectively) and length (67%, 41%, and 48%, respectively) compared to controls at 8 but not at 4 days. Glutamine, fish oil, and guar gum had no effect on ulcer healing at 4, 8, or 14 days. Among the histological parameters, a significant decrease in crypt length in the yeast RNA-supplemented group at 8 days suggested an acceleration of the healing process and restoration to a near-normal crypt-villous architecture. We conclude that the yeast RNA, arginine, and yeast RNA + arginine diets accelerated ulcer healing, as indicated by decreased ulcer number and length. We postulate that the underlying mechanism(s) contributing to ulcer healing may be related, in part, to increased cell proliferation.
Adenosine increased the DNA synthesis rate and the percentage of S-phase cells 2-3-fold in mouse mammary epithelial cells (NMuMG), with an optimum concentration of 10-100 microM. This effect was not mimicked by adenosine metabolites adenine, hypoxanthine, or inosine. N-ethylcarboxamidoadenosine (NECA, a relatively nonselective adenosine receptor agonist) and 2-p-(2-carboxyethyl) phenethylamino-5'-N ethylcarbox-amidoadenosine (CGS-21680, an A2 selective agonist) also increased DNA synthesis by mammary epithelial cells. However, N6-cyclohexyladenosine (CHA, an agonist for A1 type receptors) decreased DNA synthesis. The A1 selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) had no effect on basal or adenosine-induced DNA synthesis, whereas the A2 selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) decreased adenosine-induced DNA synthesis. Similar effects were observed in another nontumorigenic mouse mammary epithelial line, HC11, as well as the nontumorigenic human lines MCF-10A and 184.A1. Binding studies indicated that NMuMG cells contained approximately 3200 A1 receptors and about 5300 A2 receptors per cell. Both CGS-21680 and CHA increased GTPase activity in isolated cell membranes, whereas only CGS-21680 increased activity of adenylyl cyclase. Adenosine and CGS-21680 increased expression of a cyclic AMP responsive reporter gene. In addition, the protein kinase A inhibitor H-89 blocked the ability of adenosine and CGS-21680 to induce DNA synthesis, but did not affect EGF-induced DNA synthesis. These results indicate that adenosine appears to be a possible growth promoting agent in mammary tissue, and this effect may be mediated by extracellular receptors of the A2 type.
The optimal concentration of a human placental polydeoxyribonucleotide (PDRN) preparation (100 microg/ml) enhances the growth of human corneal fibroblasts in primary culture depending upon the donor age. In particular, this effect is very consistently reproducible with donors over 60 years of age (p = 0.0028), suggesting a selective benefit of PDRN in the tissue culture of senescent cells. Moreover, this drug may promote the development of human iris pigment epithelium (IPE) cells with much lower concentrations of fetal bovine serum than those suitable for the culture of IPE. Lastly, the use of a 'gauze disk' on the pieces of the corneal explants improves the efficiency of growth of the control fibroblast primary cultures.
Several researchers have recently shed new light upon the importance of extracellular nucleotides and nucleosides to stimulate cells growth. PDRN, a mixture of deoxyribonucleotides polymers of different lengths, has recently demonstrated to stimulate "in vitro" fibroblast proliferation and collagen production, probably stimulating the purinergic receptor system. In this work we evaluated the effects of PDRN on human cultured osteoblasts, focusing our attention on cell proliferation and alkaline phosphatase activity. PDRN at a concentration of 100 microg/ml induce an increase in osteoblasts growth after 6 days as compared to control (+21%). The addition of DMPX 50 microM and suramine (P2 inhibitor) 10 microM give different results: suramine has no significant effect, while DPMX reduce, even if partially, the PDRN induced cell growth. The alkaline phosphatase activity shows a gradual enhancement starting from day 0 to day 10, even if PDRN treated cells, examined at day 6, present a sensibly lower phosphatase activity when compared to controls. Our data demonstrate that PDRN acts as an osteoblast growth stimulator. Its action is partially due to a stimulation of the purinergic system mediated by A2 purinoreceptors, however we can not exclude the involvement of other mechanism like salvage pathway.
The effect of polydeoxyribonucleotide (PDRN) eye drops vs placebo on corneal epithelial healing after photorefractive keratectomy (PRK) for correction of myopic and myopic-astigmatic defects was evaluated in a randomized, double-blind clinical trial. Primary endpoint for efficacy was the evolution of corneal re-epithelialization. Secondary endpoint was the evaluation of PDRN eye drops tolerability.
Sixty eyes were enrolled in the study, randomly allocated into standard therapy plus placebo eye drops (30 eyes), or standard therapy plus PDRN eye drops (30 eyes). Checks were carried out preoperatively and at days 1, 2, 3, and 7 of the follow-up. Six eyes dropped out (four in PDRN group, two in placebo group) for reasons unrelated to the study.
On day 2, the disepithelialized area was 8.4 mm2+/-9.2 (mean+/-SD) in controls and 6.0 mm2+/-6.8 in PDRN group. On day 3 a complete corneal re-epithelialization was found in 20 out of 26 (77%) eyes of PDRN group and in 17 out of 28 (61%) eyes of placebo group (p<0.05 in percentage terms). On day 7 of follow-up, all eyes appeared to be completely re-epithelialized. The mean score of corneal evaluation on day 3 was 2.9 in PDRN group and 3.75 in control group (p<0.05 between groups). No adverse events occurred during the study.
The data of the study have shown that after PRK, PDRN stimulates corneal epithelium regeneration. PDRN eye drops administration four times a day is well tolerated by patients during the re-epithelialization stage. A much larger clinical study should be performed in order to prove the results obtained in this pilot study.