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Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine

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Burns & Trauma 2021年第1期9卷 288-298页

作者： Jinxiu Yang Shiyi Li Leren He Minliang Chen Department of Burn and Plastic Surgery the Fourth Medical CentreChinese People’s Liberation Army General HospitalNo.51 Fucheng RoadHaidian DistrictBeijing100038China Chinese People’s Liberation Army General Hospital No.28 Fuxing RoadHaidian DistrictBeijing100853China 7th Department of Plastic Surgery Plastic Surgery HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNo.33 Ba Dachu RoadShi Jingshan DistrictBeijing100144China

Background:The clinical features of keloids consist of aberrant proliferation,secretion,differentiation and apoptosis of keloid dermis-derived fibroblasts(KFBs).Notably,the apoptosis rate of KFBs is lower than the proliferation *** the anti-fibrotic effect of adipose-derived stem cells(ADSCs)on keloids has become a hot topic of research,the exact anti-fibrotic mechanism of the paracrine effect remains *** study aimed to find out how the conditioned medium of ADSCs(ADSC-CM)exerts an anti-fibrotic effect in ***:KFBs and ADSCs were extracted and ***,ADSC-CM was *** ADSC-CM could inhibit KFB growth and induce apoptosis was verified by the use of a cell counting kit-8,an 5-Ethynyl-2-deoxyuridine(Edu)kit and flow *** expressions of cyclooxygenase-1(COX-1),COX-2,caspase 3 and B-cell lymphoma-2(Bcl-2)in ADSC-CM-cultured KFBs were tested by real-time PCR and western *** clarify the role of COX-2 in ADSC-CM-induced KFB apoptosis,a specific COX-2 inhibitor,celecoxib,was applied to KFBs cultured in ***,we tested the production of arachidonic acid(AA)and prostaglandin E2(PGE2)by ***,we established a keloid transplantation model in a nude mouse to validate the therapeutic effect in ***:The proliferation ability of KFBs cultured in ADSC-CM was found to be weakened and apoptosis was significantly *** 3 expression was significantly upregulated and Bcl-2 was downregulated in ADSC-CM-cultured ***,ADSC-CM strikingly elevated COX-2 mRNA and protein expressions,but COX-1 expression was ***-2 inhibitors reduced ADSC-CM-induced ***,COX-2 inhibition blocked the elevation of caspase 3 and reversed the decrease in Bcl-2 ***-CM increased PGE2 levels by 1.5-fold and this effect was restrained by COX-2 *** the nude mouse model,expressions of AA,COX-2 and PGE2 were higher in the translated keloid tissues after ADSC-CM injecti

关键词： keloids Adipose-derived stem cells Fibroblasts Apoptosis Anti-fibrosis cyclooxygenase-2 Arachidonic acid

Scar-centered dilation in the treatment of large keloids

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World Journal of Clinical Cases 2022年第18期10卷 6032-6038页

作者： Min Wu Jie-Yu Gu Ran Duan Bo-Xuan Wei Feng Xie Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai JiaoTong University School of MedicineShanghai 200011China

BACKGROUND Hypertrophic scars and keloid treatment is a major problem in plastic *** small keloids can be treated with resection followed by radiotherapy,large keloids require treatment with a tissue *** methods increase the need for auxiliary incisions,causing new scar *** To introduce a new method for the treatment of keloids with an *** Between 2018 and 2021,we performed surgeries to treat large keloids in nine patients with a two-stage *** the first stage,an intrascar incision was made in the keloid,and a customized expander was implanted under the keloid and the surrounding normal skin.A period of 3-6 mo was allowed for skin *** the second stage,after the initial incision healed,a follow-up surgery was performed to remove the expander,resect the keloid,and repair the expanded skin *** accomplish this,an incision was made along the scar boundary to avoid making a new surgical incision and creating new *** radiotherapy was then performed *** Two patients had anterior chest *** treatment,the anterior chest incision was broken repeatedly and then sutured again after *** healed smoothly without scar *** were successfully removed in 7 patients without *** This method was performed through a keloid incision and with a custom expander *** full expansion,the keloid was directly resected using a linear suture,which avoids new surgical incisions and scars and can successfully remove large-area *** treatment is effective,providing new insights and strategies for the treatment of similar large-area keloid and hypertrophic scar cases in the future.

关键词： Expander keloids Superficial radiotherapy Intrascar incision Treatment

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Chinese Journal of Plastic and Reconstructive Surgery 2022年第1期4卷 44-48页

作者： Yating Yang Zongan Chen Xiaoli Wu Wei Liu Zhen Gao Department of Plastic and Reconstructive Surgery Shanghai Tissue Engineering Key LaboratoryShanghai Research Institute of Plastic and Reconstructive SurgeryShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

keloids are a fibroproliferative disorder of the skin and can cause physical discomfort and psychological *** from local factors such as skin tension and infection,increasing evidence has suggested that systemic endocrine factors also contribute to the emergence and development of *** disorders have long been suspected to be a risk factor;however,previous studies have mainly focused on the role of female hormones and neglected the critical role of male *** we reviewed the published literature addressing sex steroids in pathological scars,we speculated that androgens(i.e.,male hormones)could become actively involved through sebum-associated hypersensitivity reactions and acne-derived skin lesions,resulting in persistent cutaneous *** hypothesis was also supported by previous in vitro studies,in which elevated androgen levels and androgenic receptors were detected in keloid ***,relief of pain and pruritus has been observed in patients with keloids who accidently received anti-androgen treatment for other irrelevant ***,we propose that androgen-related disorders are critical in the pathogenesis of keloids,and systemic treatment targeting sex hormones may provide long-term benefits for predisposed patients with multiple keloids.

关键词： keloids Androgen Sebum Inflammation Systemic treatment

The Effects of Laser Therapy in Treating Hypertrophic Scars and keloids after Median Sternotomy:A Scoping Review

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Congenital Heart Disease 2024年第4期19卷 363-374页

作者： Laura Schianchi Fabrizio Vaira Massimo Chessa Serena Francesca Flocco Arianna Magon Gianluca Conte Karina Geraldina Zuniga Olaya Giacomo Bortolussi Erika Cioffi Matteo Riccardo Di Nicola Santo Raffaele Mercuri Rosario Caruso Adult Congenital Heart Disease Unit IRCCS Policlinico San DonatoSan Donato MilaneseMilan20097Italy Dermatology and Cosmetology Unit IRCCS Ospedale San RaffaeleMilan20132Italy Faculty of Medicine and Surgery Vita-Salute San Raffaele UniversityMilan20132Italy Health Professions Research and Development Unit IRCCS Policlinico San DonatoSan Donato MilaneseMilan20097Italy Department of Congenital Cardiac Surgery IRCCS Policlinico San DonatoSan Donato MilaneseMilan20097Italy Cardiac Surgery IRCCS Policlinico San DonatoSan Donato MilaneseMilan20097Italy Department of Biomedical Sciences for Health University of MilanMilan20133Italy

Background:Hypertrophic scars and keloids,common complications following median sternotomy for cardiac surgery,signiﬁcantly impact patient quality of life due to their aesthetic and symptomatic *** advancements in laser therapy have made it a prominent option for managing these complex scars,yet a com-prehensive understanding of its efﬁcacy is *** aim of this scoping review is to explore the effects of laser therapy in managing hypertrophic scars and keloids after median ***:This scoping review ana-lyzed studies up to February 2024 from databases including PubMed,EMBASE,CINAHL,Scopus,Web of Science,and the Cochrane *** included any study that assessed laser therapy’s effects on hypertrophic scars and keloids following median *** were selected based on predeﬁned inclusion criteria with-out publication year,design,or origin ***:Six studies met the inclusion criteria,involving a total ofﬁve RCTs and one *** studies primarily tested 585 and 595-nm pulsed dye laser(PDL)treatments,focusing on scar appearance,patient symptoms,and treatment *** studies reported signiﬁcant improvements in scar height reduction and patient symptom relief after treatment,with mixed results for scar erythema and *** events were generally mild and ***:Laser therapy offers a beneﬁcial approach for improving the appearance and symptoms of hypertrophic scars and keloids post-median ***,further research is necessary to optimize treatment parameters and explore the long-term psychosocial impacts of this *** review highlights the need for more comprehensive studies to establish standardized treatment protocols and evaluate their effectiveness.

关键词： Laser therapy hypertrophic scars keloids median sternotomy cardiac surgery pulsed dye laser scar management

Concurrent Multi-Modality Treatment of keloids (CMTK) Not Manageable by Conventional Postoperative Radiotherapy

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International Journal of Clinical Medicine 2013年第5期4卷 273-281页

作者： Kamal Malaker Mustafa Zaidi Mohamad Rida Franka Tawfik Al Yafi Burns and Plastic Surgery Centre Burns and Plastic Surgery Hospital Tripoli Libya Introduction to Clinical Medicine Ross University School of Medicine Roseau Dominica Plastic Surgery King Khalid National Guard Hospital Jeddah KSA

Objective: To design and test a treatment regimen which is clinically responsive, readily available, cost effective, and applicable especially to children and women of child bearing age. Design Setting: A prospective cohort study. Setting: Two major postgraduate teaching hospitals: one in Tripoli, Libya and the other in Jeddah, Saudi Arabia. Participants: Fifty-seven patients with 79 keloids, referred from Plastic Surgery Units between April 1996 and January 2005. Main Outcome Measure: Degree of flattening of the keloidal lesion and symptomatic recovery. Results: Result of treatment has been analyzed using unified set criteria. Seventy-seven percent of this cohort had complete response. 19% of cases had partial response, 50% acknowledged the treatment outcome had been “satisfactory” and 44% had an “acceptable” outcome. There was no significant acute or delayed reaction. Conclusion: The technique appears universally adaptable, cost effective, and can safely be prescribed for children and women of child-bearing age. In spite of prolonged treatment course, compliance was excellent.

关键词： Unresceptable keloids Non-Surgical Treatment

A Network Pharmacology Study on Active Components and Targets of Citri Reticulatae Pericarpium for Treating keloids

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Medicinal Plant 2024年第1期15卷 18-23,31页

作者： Chang REN Ru CHEN Lei SONG Kun GUO Liying QIU College of Pharmacy Southwest Minzu UniversityChengdu 610041China

[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium."Keloid"was used as key word to search for related therapeutic targets from Drug Bank,OMIM,TTD,and GEO *** Chinese medicine compound-target network was constructed by Cytoscape ***,gene ontology(GO)and Kyoto Encyclopedia of genes and genome enrichment analysis were also ***,Discovery Studio software was used to assess the interaction of key components and genes.[Results]Five active components of Citri Reticulatae Pericarpium,773 compound targets and 676 keloid treatment targets were obtained in the *** the intersection,there are 47 targets of Citri Reticulatae Pericarpium for treating *** genes were identified such as MMP9,IL6,TNF,TP53,and VEGFA,which were enriched in tumor necrosis factor-α,nuclear factor kappa-B,and other signaling *** molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium.[Conclusions]Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling *** present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids.

关键词： Network pharmacology keloids Citri Reticulatae Pericarpium

The radiation therapy in keloids treatment: a comprehensive review of pathomechanism, damage mechanisms and cellular response

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Plastic and Aesthetic Research 2017年第7期4卷 116-126页

作者： Jing Xu Elan Yang Nan-Ze Yu You-Bin Wang Xiao Long Peking Union Medical College Beijing 100730China Department of Plastic Surgery Peking Union Medical College HospitalBeijing 100730China

Keloid management has always been frustrating and challenging. The combination therapy of surgical excision and radiation therapy was deemed as the last resort for decades. The authors performed a thorough and comprehensive review over the mechanisms on how radiation therapy damages the keloid cells. The keloid cells' cellular response towards damage induced by irradiation was also studied based on original and current literatures. Mechanisms of damage generated by radiation therapy on keloid cells remained partially understood. However, direct damage was identified playing dominant role, in contrast to damage involved cancer cell apoptosis. Moreover, the p53 pathway and some inflammatory factors like interleukin-6 were believed to function in cellular response to irradiation. However, the transforming growth factor beta, which was the major dysregulated pathway involved in pathogenesis of keloid formation showed no apparent correlation with cellular response to irradiation damage. These pathways could partially explain radiation resistance in some refractory keloid lesions. The scientific basis and experimental proof in this field was still inadequate, which drove us to find more evidence to identify the key regulator response to damage engendered by radiation therapy. Further pathway identification may benefit the drug development to prevent keloid recurrence.

关键词： Radiation therapy keloids combination therapy

Possible Mechanisms and Prospects of Stem Cell Therapy for keloids

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International Journal of Dermatology and Venereology 2019年第3期2卷 160-164页

作者： Min-Min Zhang Xiao-Dong Chen Medical School Nantong UniversityNantongJiangsu 226001China Department of Dermatology Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China

Introduction keloids are a benign proliferative disease of the skin caused by abnormal healing of physiological *** are similar to hypertrophic ***,keloids extend beyond the margin of the original wound and do not spontaneously regress,while hypertrophic scars are confined to the original wound and generally maintain their shape.1 keloids cause pain,pruritus,restricted joint activity and cosmetic problems,and negatively affect quality of *** bioactivity of keloids is regulated by various factors,such as transforming growth factor (TGF)-β,connective tissue growth factor (CTGF),and hypoxia inducible factor (HIF).2-4 These inflammatory factors are involved in keloid fibrosis,collagen production,and the deposition of extracellular ***,the pathogenesis of keloids remain unclarified,and it is still one of the most challenging diseases in clinical practice.

关键词： Possible Mechanisms Stem Cell keloids

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Advances in postoperative radiotherapy for keloids

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International Journal of Dermatology and Venereology 2018年第4期1卷 212-216页

作者： Rong Li Jia-An Zhang Kun Chen Department of Physiotherapy Hospital for Skin Disease (Institute of Dermatology) Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing Jiangsu 210042 China

Introduction keloids, a type of skin lesion that presents as patho-logically excessive dermal fibrosis and aberrant wound healing, are caused by cell proliferation and hyaline degeneration of connective tissues. The specific pathogenesis of keloids is still unknown(1-2)There are multiple therapeutic strategies for keloids, including surgery, cryotherapy, laser or light-based therapy, and intralesional corticosteroid injection. However, none of these is optimal. Surgical excision combined with adjuvant radiation is considered to be a safer and more efficacious method(3)From publicly available data, the recurrence rate of keloids after simple surgical excision amounts to 45%-100%(4)Based on published reports, postoperative radiotherapy results in a control rate of 67%- 81%, and the recurrence rate decreases to 24.5%-35%(4-12)This article reviews papers related to postoperative radiotherapy treatment for keloids, and also discusses radiation types, parameters, safety and effectiveness.

关键词： keloids patho-logically excessive dermal fibrosis