The use of human adipose-derived stem cells in the treatment of physiological and pathological vulvar dystrophies

“Vulvar dystrophy” is characterized by chronic alterations of vulvar trophism, occurring in both physiological (menopause) and pathological (lichen sclerosus, vulvar graft-versus-host disease) conditions. Associated symptoms are itching, burning, dyspareunia and vaginal dryness. Current treatments often do not imply a complete remission of symptoms. Adipose-Derived Stem Cells (ADSCs) injection represents a valid alternative therapy to enhance trophism and tone of dystrophic tissues. We evaluated efficacy of ADSCs-based therapy in the dystrophic areas. From February to April 2013 we enrolled 8 patients with vulvar dystrophy. A biopsy specimen was performed before and after treatment. Digital photographs were taken at baseline and during the follow-up. Pain was detected with Visual Analogue Scale and sexual function was evaluated with Female Sexual Function Index. All patients received 2 treatments in 3 months. Follow-up was at 1 week , 1 and 3 months, and 1 and 2 years. We obtained a significant vulvar trophism enhancement in all patients, who reported pain reduction and sexual function improvement. Objective exam with speculum was easy to perform after treatment. We believe ADSCs-based therapy finds its application in the treatment of vulvar dystrophies, since ADSCs could induce increased vascularization due to their angiogenic properties and tissue trophism improvement thanks to their eutrophic effect

Improvement of mouth functional disability in systemic sclerosis patients over one year in a trial of fat transplantation versus adipose-derived stromal cells

Background. Systemic sclerosis (SSc) is a multisystem disease characterized by cutaneous and visceral fibrosis. Face and mouth changes include telangiectasia, sicca syndrome, and thinning and reduction of mouth width (microcheilia) and opening (microstomia). We applied autologous fat transplantation compared with autologous adipose-derived stromal cells (ADSCs) injection to evaluate the clinical improvement of mouth opening. Methods. From February to May 2013 ten consecutive SSc patients were enrolled from the outpatient clinic of Plastic Surgery Department of Sapienza University of Rome. Patients were divided into two groups as follows: 5 patients were treated with fat transplantation and 5 patients received infiltration of ADSCs produced by cell factory of our institution. To value mouth opening, we use the Italian version of Mouth Handicap in Systemic Sclerosis Scale (IvMHISS). Mouth opening was assessed in centimetres (Maximal Mouth Opening, MMO). In order to evaluate compliance and physician and patient satisfaction, we employed a Questionnaire of Satisfaction and the Visual Analogic Scale (VAS) performed before starting study and 1 year after the last treatment. Results and Conclusion. We noticed that both procedures obtained significant results but neither one emerged as a first-choice technique. The present clinical experimentation should be regarded as a starting point for further experimental research and clinical trials

Nuove strategie terapeutiche nel trattamento delle ferite difficili

Introduzione. Il trattamento medico-chirurgico delle ferite difficili rappresenta un problema socio-sanitario in continua crescita, colpendo attualmente nel nostro Paese circa 2.000.000 di persone. La “ferita difficile” non è altro che una perdita di sostanza cutanea, a patogenesi multifattoriale, che non tende alla guarigione in modo spontaneo. Numerosi studi presenti in letteratura hanno evidenziato che l’uso delle medicazioni avanzate consente di raggiungere migliori risultati clinici ed economici nel processo di guarigione delle ferite difficili, assicurando sia una permanenza superiore sulla lesione che accorciando il tempo di trattamento, in quanto viene richiesto un minor numero di applicazioni rispetto alle medicazioni tradizionali. La Wound Bed Preparation (WBP) può essere definita come la gestione globale e coordinata della lesione cutanea atta a rimuovere le barriere locali alla guarigione o a promuovere l’efficacia di misure terapeutiche innovative. La medicazione avanzata non è altro che un materiale di copertura che possiede caratteristiche di biocompatibilità. Scopo della medicazione avanzata è quello di creare l’ambiente ideale per il processo di cicatrizzazione isolando la ferita da eventuali traumi ed infezioni esterne. Pazienti e metodi. Nell’Ambulatorio “Ferite Difficili” della Cattedra di Chirurgia Plastica e Ricostruttiva del Policlinico Umberto I di Roma, dal gennaio al dicembre 2006, sono stati trattati 570 pazienti (308 uomini – 262 donne), con un’età variabile dai 2 giorni agli 85 anni, affetti da ulcere di varia natura. Nell’ambito dei nostri casi clinici sono stati selezionati 200 soggetti divisi casualmente in due gruppi: gruppo A - 100 pazienti trattati unicamente con medicazioni tradizionali; gruppo B - 100 pazienti trattati unicamente con medicazioni avanzate. Ogni paziente è stato trattato localmente con medicazioni periodiche, specifiche a seconda del tipo di ferita difficile presentata. Inoltre si è proceduto all’individuazione ed alla cura dei fattori sistemici, concause dell’ulcera. Il nostro protocollo prevedeva medicazioni due o tre volte alla settimana a seconda che si trattasse di ferite infette o non infette, per un periodo cha poteva variare da un mese per i casi meno gravi ad un anno per le forme croniche. Risultati. È risultata evidente una più alta percentuale di guarigione ottenuta attraverso l’utilizzo delle medicazioni avanzate. Nel Gruppo A si sono ottenuti i seguenti risultati: la guarigione del 53% delle ferite; il restante 47% non è guarito, ma nel 17%, le medicazioni sono state di ausilio alla preparazione del letto vascolare per l’esecuzione di un intervento definitivo (applicazione di innesti o lembi locali); nel rimanente 30%, invece, è stato ottenuto solo un modestissimo miglioramento della lesione che è ancora in fase di trattamento. Nel Gruppo B si è ottenuta la guarigione del 65% delle ferite; nel restante 35% non guarito, nel 15% le medicazioni sono state di ausilio alla preparazione del letto vascolare per l’esecuzione di un intervento definitivo (applicazione di innesti o lembi locali) mentre nel rimanente 20% si è raggiunto comunque un notevole miglioramento della lesione (con riduzione delle dimensioni, scomparsa dell’infezione e miglioramento della qualità di vita del paziente). Discussione e conclusioni. In sintesi, emerge che le medicazioni avanzate, se correttamente impiegate, offrono vantaggi in termini di efficacia clinica (velocità di guarigione della lesione), di qualità della vita del paziente e di economicità. Non ultimo è da considerare che la ferita difficile è spesso l’epifenomeno di una malattia sistemica. La ferita difficile richiede, quindi, un trattamento multidisciplinare. difficile richiede, quindi, un trattamento multidisciplinare. Results. The results showed a higher percentage of recovery reached by using the advanced dressings. Group A showed the followings results: the 53% of patients recovered from wounds; the remaining 47% patients did’nt not recover but in 17% cases medications showed to be of some help in the preparation of the vascular bed for the execution of a definitive operation (application of grafts or local edges), while the remaining 30% has shown a scarce improvement of the injury and they are still under treatment. Group B showed the 65% of patients recovered from wounds; as for the remaining 35% not recovered patients, medications represented an auxiliary aid to the preparation of the vascular bed for the execution of a definitive operation (application of grafts or local edges) for the 15% of patients, while the remaining 20%, even if not completely recovered, showed a notable improvement of the injury (reduction of the dimensions and disappearance of the infection and improvement of the patient quality of life). Conclusions. In synthesis, it emerges that the advanced dressings, if correctly used, offer advantages in terms of clinical effectiveness (rapid recovery from the injury), patient quality of the life and cheapness. It has also to be considered that the difficult wound is often the epiphenomenon of a systemic illness. The difficult wound requires, therefore, a multidisciplinary treatment

Acquired ptosis associated with oculomotor and contralateral facial nerve synkinesis: the first reported case

Evidence of oculomotor nerve (ON) synkinesis is a common occurrence following both acquired and congenital III nerve palsy. It is generally accepted that aberrant regeneration is the likely aetiology of synkinesis in acquired III nerve palsy, following intracranial aneurysm, trauma, compressive neoplasms, cavernous sinus thrombosis and basilar meningitis

Trattamento della contrattura capsulare da impianto protesico mammario. Nostra esperienza

La più comune complicanza in pazienti sottoposte ad intervento chirurgico di impianto protesico mammario è la contrattura capsulare. Non esiste, attualmente, un trattamento standard efficace per questa complicanza. Lo scopo del presente articolo è illustrare la nostra esperienza sull’uso degli antagosisti dei recettori per i leucotrieni nel trattamento della contrattura capsulare. I risultati mostrano che l’utilizzo di questi farmaci è in grado di ridurre il dolore e la distorsione della mammella in pazienti con un lungo decorso di contrattura capsulare

Neuropilin 1mediates keratinocyte growth factor signaling in adipose-derived stem cells: potential involvement in adipogenesis

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs

Successful Management of a Chronic Refractory Leg Ulcer in an Adolescent with Sickle Cell Anemia

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by a wide range of clinical manifestations. Chronic leg ulcers are a disabling complication with repercussions on the quality of life. We report the case of a 14-year-old girl with a diagnosis of SCD who developed a chronic leg ulcer that was successfully treated with a multi-disciplinary approach, including local and systemic therapies. The role of different treatments, in particular low molecular weight heparin, in the refractory chronic leg ulcer healing process will be discussed. </p

MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms

Adipose-derived mesenchymal stem cells (ASCs) are promising therapeutic tools in regenerative medicine because they possess self-renewal, differentiation and immunomodulatory capacities. After isolation, ASCs are passaged multiple times in vitro passages to obtain a sufficient amount of cells for clinical applications. During this time-consuming procedure, ASCs become senescent and less proliferative, compromising their clinical efficacy. Here, we sought to investigate how in vitro passages impact ASC proliferation/senescence and expression of immune regulatory proteins. MicroRNAs are pivotal regulators of ASC physiology. Particularly, miR-200c is known to maintain pluripotency and targets the immune checkpoint Programmed death-ligand 1 (PD-L1). We therefore investigated its involvement in these critical characteristics of ASCs during in vitro passages. We found that when transiently expressed, miR-200c-3p promotes proliferation, maintains stemness, and contrasts senescence in late passaged ASCs. Additionally, this miRNA modulates PD-L1 and Indoleamine 2,3-Dioxygenase (IDO1) expression, thus most likely interfering with the immunoregulatory capacity of ASCs. Based on our results, we suggest that expression of miR-200c-3p may prime ASC towards a self-renewing phenotype by improving their in vitro expansion. Contrarily, its inhibition is associated with senescence, reduced proliferation and induction of immune regulators. Our data underline the potential use of miR-200c-3p as a switch for ASCs reprogramming and their clinical application