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The Plastic Surgery for Localized Scleroderma: Progress in Diagnosis and Treatment and Opinions from Peking Union Medical College Hospital
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摘要: 局限性硬皮病是一种罕见的自身免疫性疾病, 其皮肤纤维化和皮下组织萎缩可导致患者外貌受损, 因此常需整形外科手术治疗。本文总结了局限性硬皮病的病理生理、术前评估、外科治疗进展与临床困境, 并分享北京协和医院的诊治经验, 以期为临床提供参考和借鉴。Abstract: Localized scleroderma is a rare auto-immune disorder characterized by inflammation and fibrosis of the skin and subcutaneous fat in the affected area, leaving aesthetic impairment to the patients.Such patients often seek plastic surgery for the treatment. This article summarizes the pathophysiology and preoperative evaluation of localized scleroderma, discusses the progress and clinical dilemma of its surgical treatment, and shares the opinions on the diagnosis and treatment of a single center in Peking Union Medical College Hospital.
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1. 局限性硬皮病
硬皮病是一种自身免疫性结缔组织病，主要分为两大类：系统性硬皮病(systemic scleroderma，SS)和局限性硬皮病(localized scleroderma，LS)。目前，有研究认为二者属于两种不同的疾病[1]。SS又称系统性硬化症(systemic sclerosis，SS)，其病变特征为皮肤硬化和内脏受累，包括肺脏、肾脏、消化系统等[2]，其皮肤纤维化常于双侧手指呈对称性分布，出现内脏纤维化者死亡率较高。LS则为良性自限性疾病，病变局限于皮肤、皮下脂肪及深层组织(筋膜、肌肉和骨骼)，无内脏器官受累[3]。LS是一种相对罕见的疾病，发病率约为3/10万[2, 4]，目前具体病因仍不明确，已知的潜在危险因素包括创伤、免疫系统紊乱、感染、有毒物质或药剂、神经源性因素等[3]。LS的发病机制复杂，可影响血管、免疫系统和细胞外基质，主要病理变化为皮肤纤维化和皮下脂肪萎缩[5-6]。炎症反应是LS疾病早期主要的病理过程，可导致血管受累[5]；新形成的胶原蛋白侵入脂肪组织，同时出现炎症浸润，破坏皮肤和皮下组织中的血管[7]；LS疾病晚期，患者皮肤出现纤维化，脂肪组织亦被取代，皮肤附属器减少，出现不同程度的颜面畸形，包括面部萎缩和色素沉着[3, 5]。
按照皮肤病损的性状，Peterson等[4]将LS分为5种临床亚型：斑块型(plaque)、全身型(generalized)、深部型(deep)、大疱型(bullous)和线型/带状(linear)。Kreuter等[8]亦将LS分为5种亚型：局限型(limited)、广泛型(limited)、线型/带状(linear)、深部型(deep)和混合亚型(mixed)。不同亚型可在同一患者中单独存在或同时出现[2]。此外，Parry-Romberg综合征(Parry-Romberg syndrome，PRS)，又称进行性半侧颜面萎缩(progressive facial hemiatro-phy，PFH)，也可累及皮下组织、肌肉、骨结构或皮肤组织，临床表现与LS颇为相似[9-10]。据文献报道，此两种疾病在约20%~37%的患者中共存[11-12]。目前关于二者关系存在3种不同的观点：(1)认为LS与PFH是截然不同的两种疾病；(2)认为LS与PFH是同一疾病的不同发展阶段，PFH可能是与线性硬皮病共存的并发症[11, 13]；(3)不涉及皮肤层的PFH病例可认为是LS的一个特殊子集，其仅累及深层组织[8]。
当前已有多种LS的潜在治疗药物，包括血管扩张剂、抗血小板药物、免疫抑制剂和胶原蛋白合成抑制剂等[5-6]。但药物治疗效果有限，并可能产生全身毒性和慢性免疫抑制等不良反应，最重要的是无法纠正已产生的面部畸形[14]。因此，出于心理和审美需求，许多患者不得不寻求整形外科治疗以改善外观[15]。
2. 颜面畸形的评估与手术适应证选择
术前对患者的病变情况进行评估，有助于了解疾病进展和评价疗效。术前可采用超声、电脑皮肤评分(在黏性透明膜上绘出皮损的硬化边缘，扫描传输至计算机，可评估单个病损情况)、激光多普勒血流仪、MRI等技术对患者的皮肤病变、皮下软组织情况进行测量和分析，判断有无合并症[16]。此外，还可采用量表评分辅助简易评估，如由LS严重程度指数和LS损伤指数共同构成的LS评估工具(localized scleroderma assessment tool，LoSCAT)，可快速有效地评估皮肤病灶的特征，但缺乏对手术方式的指导意义[17-18]。北京协和医院整形美容外科根据LS颜面美学结构的受损特点，设计了“协和局限性硬皮病面部美学指数(PUMC localized scleroderma facial aesthetic index)”，为整形美容外科治疗的评估、随访和临床研究提供了辅助工具[19]。
关于LS的手术适应证，目前仍存在一定争议。一般认为处于稳定期(病灶无进展大于6个月)的LS患者接受整形移植是安全且合适的[2, 15]。然而，有研究认为外伤和手术也是LS的高危因素[8-9]。因此，接受整形外科手术的时机不当，可能导致LS疾病恶化。为抑制术后LS的再激活，患者是否需在围术期接受药物治疗或调整药物剂量尚未明确。
3. 皮瓣移植
皮瓣移植可携带较多的自体组织，提供充足的移植材料，特别适合中重度LS患者。常用的皮瓣包括股前外侧筋膜脂肪瓣(anterolateral thigh flap，ALT)、腹股沟真皮脂肪瓣、颞浅筋膜真皮脂肪瓣(super-ficial temporal fascia flap，STF)、局部扩张皮瓣等[20]。但部分皮瓣移植手术创伤较大，对供区造成额外容积缺失，部分皮瓣存活风险高，手术难度大，手术时间长[20]。此外，皮瓣移植难以直接获取合乎外观的理想厚度，一般术后略显臃肿，影响美观，因此后期还需再次手术以修薄皮瓣[20]。皮瓣边界也常遗留线性凹痕，造成面部轮廓的连续性被破坏[20]。
ALT是临床最常用的皮瓣之一，也是临床研究中用于矫正LS引起的面部畸形最常用的皮瓣[21-23]。Wolff等[24]应用ALT修复6例LS面部凹陷畸形的患者，有效矫正了患者的颜面不对称，部分患者存在脂肪液化、创面愈合不良等并发症。该研究强调了皮瓣下垂的可能性，可能与大腿筋膜和皮下层之间的连接相对松散有关[24]。
STF修复LS引起的面部凹陷畸形时，无需吻合血管，可缩短手术时间，皮瓣存活率较高[25]。但STF的血管蒂长度有限，无法进行大范围旋转推进，覆盖面积有限，适于轻中度面部萎缩患者[26]。
皮肤软组织扩张术可提供与受区色泽、质地相近的皮肤组织，并借由局部皮瓣转移进行修复，可作为LS患者面部凹陷的治疗方法，其不足之处在于术后遗留垂直皮纹瘢痕较明显[20]，扩张器的局部压迫可能引起新的面部凹陷问题[20]。
4. 自体脂肪移植与改良新型脂肪移植
游离皮瓣移植尽管可有效矫正面部软组织容积缺损，但较大的手术创伤将遗留明显的疤痕[27-29]。与之相比，自体脂肪移植(autologous fat grafting，AFG) 具有创伤小、恢复快、外观自然等诸多优势，已广泛用于LS面部畸形矫正治疗[6, 30-31]。针对LS病灶处组织粘连紧密、可直接注射的特点，北京协和医院整形美容外科提出了“注射前先行局部粘连组织松解术”理论，于注射前采用锐性针头或小针刀在皮下均匀地穿出多个并行小隧道，充分松解粘连组织后再进行注射，可有效改善注射难度、提高注射效果，已在临床广泛应用[32]。然而临床研究证实，LS患者的脂肪保留率普遍低于健康人群，且在面部的不同区域之间亦存在显著差异[31]。笔者团队采用MRI对18例LS患者的脂肪保留情况进行定量分析，结果显示首次移植的脂肪保留率在术后6个月约为20%[33]，远低于正常人群的60%[34]。低脂肪保留率的发生可能与LS患者的局部炎症微环境、血管损伤引起局部供血不足以及脂肪细胞凋亡增加有关[31, 35-36]。
目前，普遍认为移植后的脂肪组织将进行一个动态的重塑过程，脂肪细胞的凋亡与增殖同步进行，而脂肪干细胞(adiposederived stem cells，ASCs)被认为在调节此平衡中发挥至关重要的作用[37]。与内皮细胞和ASCs相比，脂肪细胞对缺血应激的耐受性明显较差[38]。ASCs可分泌多种促血管生成相关细胞因子以促进血管生成，继而增加脂肪的存活和再生[37, 39-40]。此外，这些细胞因子还可通过促进抗凋亡蛋白、抑制促凋亡蛋白的表达参与抑制脂肪细胞凋亡的过程[39]。ASCs可在缺血条件下存活并被激活，通过增殖和分化脂肪细胞以促进脂肪组织再生[38]。北京协和医院整形美容外科比较了LS患者与健康人群体内ASCs的生物学活性，发现分离的ASCs品系在形态或成脂分化潜能上无统计学差异，但来源于具有皮质类固醇治疗史LS患者的ASCs数量显著低于健康人群和未经皮质类固醇治疗的LS患者[31]。该研究结果表明，皮质类固醇治疗可能引起ASCs耗竭，继而引起LS患者的脂肪保留率降低。
此外，一些基础研究和临床实践也证实脂肪移植对LS患者具有一定的治疗作用，包括改善皮肤纤维化和减少色素沉着等[6, 31, 41-42]。动物实验研究证实，对博来霉素诱导的皮肤纤维化裸鼠模型进行脂肪移植后，裸鼠皮肤内胶原蛋白的含量降低[31]。在一些使用脂肪移植治疗皮肤硬化症的临床研究中也观察到类似现象[43-44]。此现象可能与移植脂肪组织中的ASCs旁分泌功能有关。在诸如LS的炎性微环境中，ASCs可能通过其免疫调节作用抑制局部炎症反应，继而改善组织结构[31]。但ASCs对皮肤纤维化的调节涉及复杂的机制，对其进行深入研究对于细胞疗法在调控皮肤纤维化领域的应用具有积极意义[42]。
为弥补ASCs的不足并改善脂肪保留率，新型脂肪移植方法被用于治疗LS患者，包括血管基质成分(stromal vascular fraction，SVF)辅助移植、富血小板血浆(platelet-rich plasma，PRP)辅助移植、纳米脂肪移植(nanofat grafting)和离体扩增ASCs移植。目前，尚无证据证实SVF辅助移植法可产生相当于或高于2次常规脂肪移植的脂肪保留率[45]。一项研究比较了LS患者与健康受试者来源的SVF的分子和功能特征，结果显示尽管LS患者的SVF保留了血管生成能力，但SVF形成的新血管密度与健康受试者相比略有下降[46]。Virzi等[47]采用PRP与SVF联合脂肪移植治疗硬皮病，结果显示患者面部皮肤病变改善，但未测试脂肪保留是否增加。Serratrice等[48]比较了纳米脂肪移植与其他辅助移植方式(包括SVF和PRP辅助移植)在LS小鼠模型中的功效，结果显示所有方法均对LS皮肤纤维化病变和血管损伤有不同程度的改善效果。此外，不同于传统脂肪移植或SVF、PRP辅助的脂肪移植，纳米脂肪移植可逆转皮肤纤维化[48-49]。由于SVF和PRP的组成、ASCs的数量以及这些细胞的活性在患者之间存在巨大差异，导致上述细胞富集方法的性质难以预测，因此有学者尝试采用离体扩增ASCs移植法[45, 48]，该方法不仅可获得足够的干细胞，还可鉴定移植前的ASCs生物学活性[50]。研究证实，采用离体扩增ASCs移植法治疗PFH患者，ASCs组的脂肪总体保留率超过70%，明显高于常规治疗组(54%)[51-52]。
5. 小结
LS是一种可导致颜面部畸形的自身免疫性疾病，皮瓣移植与自体脂肪移植已在其治疗中得到广泛应用，特别是脂肪移植具有改善美观和治疗效果的作用，但其低脂肪保留率问题尚待解决。目前已提出一系列新型脂肪移植方法，主要利用ASCs的生理特性对传统的脂肪移植方式进行改良，在基础和临床研究领域取得了一定进步，可能有助于解决低脂肪保留率这一棘手问题。此外，ASCs对皮肤纤维化的调节亦具有一定治疗意义，显示出细胞疗法在皮肤纤维化、自身免疫性疾病治疗等领域具有巨大的应用潜力。
作者贡献：王晨羽负责资料收集、初稿撰写；龙笑、曾昂、黄久佐、王晓军负责经验总结、资料提供，参与初稿撰写；龙笑负责文章修订。利益冲突：所有作者均声明不存在利益冲突 -
[1] Toki S, Motegi S, Yamada K, et al. Clinical and laboratory features of systemic sclerosis complicated with localized scleroderma[J]. J Dermatol, 2015, 42: 283-287. DOI: 10.1111/1346-8138.12775
[2] Distler O, Cozzio A. Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy[J]. Semin Immunopathol, 2016, 38: 87-95. DOI: 10.1007/s00281-015-0551-z
[3] Careta MF, Romiti R. Localized scleroderma: clinical spectrum and therapeutic update[J]. An Bras Dermatol, 2015, 90: 62-73.
[4] Peterson LS, Nelson AM, Su WP. Classification of morphea (localized scleroderma)[J]. Mayo Clin Proc, 1995, 70: 1068-1076. DOI: 10.4065/70.11.1068
[5] Valanciene G, Jasaitiene D, Valiukeviciene S. Pathogenesis and treatment modalities of localized scleroderma[J]. Medicina (Kaunas), 2010, 46: 649-656. DOI: 10.3390/medicina46100092
[6] Strong AL, Rubin JP, Kozlow JH, et al. Fat Grafting for the Treatment of Scleroderma[J]. Plast Reconstr Surg, 2019, 144: 1498-1507. DOI: 10.1097/PRS.0000000000006291
[7] Rongioletti F, Ferreli C, Atzori L, et al. Scleroderma with an update about clinico-pathological correlation[J]. G Ital Dermatol Venereol, 2018, 153: 208-215.
[8] Kreuter A, Krieg T, Worm M, et al. [AWMF Guideline no. 013/066. Diagnosis and therapy of circumscribed scleroderma][J]. J Dtsch Dermatol Ges, 2009, 7: S1-S14.
[9] Blaszczyk M, Krolicki L, Krasu M, et al. Progressive facial hemiatrophy: central nervous system involvement and relationship with scleroderma en coup de sabre[J]. J Rheumatol, 2003, 30: 1997-2004.
[10] El-Kehdy J, Abbas O, Rubeiz N. A review of Parry-Romberg syndrome[J]. J Am Acad Dermatol, 2012, 67: 769-784. DOI: 10.1016/j.jaad.2012.01.019
[11] Tollefson MM, Witman PM. En coup de sabre morphea and Parry-Romberg syndrome: a retrospective review of 54 patients[J]. J Am Acad Dermatol, 2007, 56: 257-263. DOI: 10.1016/j.jaad.2006.10.959
[12] Zulian F, Athreya BH, Laxer R, et al. Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study[J]. Rheumatology (Oxford), 2006, 45: 614-620. DOI: 10.1093/rheumatology/kei251
[13] Lehman TJ. The Parry Romberg syndrome of progressive facial hemiatrophy and linear scleroderma en coup de sabre. Mistaken diagnosis or overlapping conditions?[J]. J Rheumatol, 1992, 19: 844-845.
[14] Noh JW, Kim J, Kim JW. Localized scleroderma: a clinical study at a single center in Korea[J]. Int J Rheum Dis, 2013, 16: 437-441. DOI: 10.1111/1756-185X.12080
[15] Wang HC, Dong R, Long X, et al. Aesthetic and therapeutic outcome of fat grafting for localized Scleroderma treatment: From basic study to clinical application[J]. J Cosmet Dermatol, 2021, 20: 2723-2728. DOI: 10.1111/jocd.13941
[16] Gabrielli A, Avvedimento EV, Krieg T. Scleroderma[J]. N Engl J Med, 2009, 360: 1989-2003. DOI: 10.1056/NEJMra0806188
[17] Arkachaisri T, Vilaiyuk S, Li S, et al. The localized scleroderma skin severity index and physician global assessment of disease activity: a work in progress toward development of localized scleroderma outcome measures[J]. J Rheumatol, 2009, 36: 2819-2829. DOI: 10.3899/jrheum.081284
[18] Lis-Święty A, Skrzypek-Salamon A, Ranosz-Janicka I, et al. Associations between Disease Activity/Severity and Damage and Health-Related Quality of Life in Adult Patients with Localized Scleroderma-A Comparison of LoSCAT and Visual Analogue Scales[J]. J Clin Med, 2020, 9: 756. DOI: 10.3390/jcm9030756
[19] Wang HC, Ling S, Wang X, et al. The Development and Initial Validation of PUMC Localized Scleroderma Facial Aesthetic Index: A Pilot Study[J]. Aesthetic Plast Surg, 2021, 45: 1531-1539. DOI: 10.1007/s00266-020-02111-4
[20] 陈波. 脂肪干细胞辅助脂肪移植治疗局限性硬皮病的相关研究[D]. 北京: 北京协和医学院, 2017. [21] Jandali S, Mehrara B. Free anterolateral thigh perforator flap in a patient with systemic sclerosis and Raynaud's phenomenon[J]. Plast Reconstr Surg, 2006, 118: 90e-92e. DOI: 10.1097/01.prs.0000232388.59236.3a
[22] Wang TY, Serletti JM, Kolasinski S, et al. A review of 32 free flaps in patients with collagen vascular disorders[J]. Plast Reconstr Surg, 2012, 129: 421e-427e. DOI: 10.1097/PRS.0b013e3182412a0b
[23] Acarturk TO, Maldonado AA, Ereso A. Intraoral reconstruction with "thinned" peroneal artery perforator flaps: An alternative to classic donor areas in comorbid patients[J]. Microsurgery, 2015, 35: 399-402. DOI: 10.1002/micr.22366
[24] Wolff KD, Kesting M, Loffelbein D, et al. Perforator-based anterolateral thigh adipofascial or dermal fat flaps for facial contour augmentation[J]. J Reconstr Microsurg, 2007, 23: 497-503. DOI: 10.1055/s-2007-992349
[25] Terzis JK, Olivares FS. Uses of the superficial temporal fascial flap in facial paralysis[J]. Plast Reconstr Surg, 2008, 122: 176e-185e. DOI: 10.1097/PRS.0b013e31818dc012
[26] Siebert JW, Anson G, Longaker MT. Microsurgical correction of facial asymmetry in 60 consecutive cases[J]. Plast Reconstr Surg, 1996, 97: 354-363. DOI: 10.1097/00006534-199602000-00013
[27] Consorti G, Tieghi R, Clauser LC. Frontal linear scleroderma: long-term result in volumetric restoration of the fronto-orbital area by structural fat grafting[J]. J Craniofac Surg, 2012, 23: e263-e265. DOI: 10.1097/SCS.0b013e31824ef7e8
[28] Lapiere JC, Aasi S, Cook B, et al. Successful correction of depressed scars of the forehead secondary to trauma and morphea en coup de sabre by en bloc autologous dermal fat graft[J]. Dermatol Surg, 2000, 26: 793-797. DOI: 10.1046/j.1524-4725.2000.00073.x
[29] Lee JH, Lim SY, Lee JH, et al. Surgical Management of Localized Scleroderma[J]. Arch Craniofac Surg, 2017, 18: 166-171. DOI: 10.7181/acfs.2017.18.3.166
[30] Zanelato TP, Marquesini G, Colpas PT, et al. Implantation of autologous fat globules in localized scleroderma and idiopathic lipoatrophy--report of five patients[J]. An Bras Dermatol, 2013, 88: 120-123. DOI: 10.1590/abd1806-4841.20132115
[31] Chen B, Wang X, Long X, et al. Supportive Use of Adipose-Derived Stem Cells in Cell-Assisted Lipotransfer for Localized Scleroderma[J]. Plast Reconstr Surg, 2018, 141: 1395-1407. DOI: 10.1097/PRS.0000000000004386
[32] 王阳, 陈波, 王晓军. 自体脂肪移植综合技术矫正面部局限性硬皮病[J]. 组织工程与重建外科杂志, 2016, 12: 34-36. DOI: 10.3969/j.issn.1673-0364.2016.01.009 Wang Y, Chen B, Wang XJ. Application of Autologous Fat Graft in Treating Facial Localized Scleroderma[J]. Zuzhi Gongcheng Yu Chongjian Waike Zazhi, 2016, 12: 34-36. DOI: 10.3969/j.issn.1673-0364.2016.01.009
[33] Wang C, Long X, Si L, et al. A pilot study on ex vivo expanded autologous adipose-derived stem cells of improving fat retention in localized scleroderma patients[J]. Stem Cells Transl Med, 2021, 10: 1148-1156. DOI: 10.1002/sctm.20-0419
[34] Denadai R, Raposo-Amaral CA, Pinho AS, et al. Predictors of Autologous Free Fat Graft Retention in the Management of Craniofacial Contour Deformities[J]. Plast Reconstr Surg, 2017, 140: 50e-61e. DOI: 10.1097/PRS.0000000000003440
[35] Chen W, Xia ZK, Zhang MH, et al. Adipose tissue-derived stem cells ameliorates dermal fibrosis in a mouse model of scleroderma[J]. Asian Pac J Trop Med, 2017, 10: 52-56. DOI: 10.1016/j.apjtm.2016.10.005
[36] Slack GC, Tabit CJ, Allam KA, et al. Parry-Romberg reconstruction: beneficial results despite poorer fat take[J]. Ann Plast Surg, 2014, 73: 307-310. DOI: 10.1097/SAP.0b013e31827aeb0d
[37] Li Y, Zhang W, Gao J, et al. Adipose tissue-derived stem cells suppress hypertrophic scar fibrosis via the p38/MAPK signaling pathway[J]. Stem Cell Res Ther, 2016, 7: 102. DOI: 10.1186/s13287-016-0356-6
[38] Suga H, Eto H, Aoi N, et al. Adipose tissue remodeling under ischemia: death of adipocytes and activation of stem/progenitor cells[J]. Plast Reconstr Surg, 2010, 126: 1911-1923. DOI: 10.1097/PRS.0b013e3181f4468b
[39] Kato H, Mineda K, Eto H, et al. Degeneration, regeneration, and cicatrization after fat grafting: dynamic total tissue remodeling during the first 3 months[J]. Plast Reconstr Surg, 2014, 133: 303e-313e. DOI: 10.1097/PRS.0000000000000066
[40] 王晨羽, 王晓军, 龙笑. 血管化复合同种异体移植的干细胞治疗进展[J]. 中华整形外科杂志, 2021, 37: 692-695. Wang CY, Wang XJ, Long X. Stem cell therapy on vas-cular composite allotransplantation[J]. Zhonghua Zheng xing Waike Zazhi, 2021, 37: 692-695.
[41] Laloze J, Varin A, Gilhodes J, et al. Cell-assisted lipotransfer: Friend or foe in fat grafting? Systematic review and meta-analysis[J]. J Tissue Eng Regen Med, 2018, 12: e1237-e1250.
[42] Zheng H, Yu Z, Deng M, et al. Fat extract improves fat graft survival via proangiogenic, anti-apoptotic and pro-proliferative activities[J]. Stem Cell Res Ther, 2019, 10: 174. DOI: 10.1186/s13287-019-1290-1
[43] Jeon YR, Roh H, Jung JH, et al. Antifibrotic Effects of High-Mobility Group Box 1 Protein Inhibitor (Glycyrrhizin) on Keloid Fibroblasts and Keloid Spheroids through Reduction of Autophagy and Induction of Apoptosis[J]. Int J Mol Sci, 2019, 20: 4134. DOI: 10.3390/ijms20174134
[44] Kim KK, Sheppard D, Chapman HA. TGF-β1 Signaling and Tissue Fibrosis[J]. Cold Spring Harb Perspect Biol, 2018, 10: a022293. DOI: 10.1101/cshperspect.a022293
[45] Rasmussen BS, Lykke Sorensen C, Vester-Glowinski PV, et al. Effect, Feasibility, and Clinical Relevance of Cell Enrichment in Large Volume Fat Grafting: A Systematic Review[J]. Aesthet Surg J, 2017, 37: S46-S58. DOI: 10.1093/asj/sjx008
[46] Magalon J, Velier M, Simoncini S, et al. Molecular profile and proangiogenic activity of the adipose-derived stromal vascular fraction used as an autologous innovative medicinal product in patients with systemic sclerosis[J]. Ann Rheum Dis, 2019, 78: 391-398. DOI: 10.1136/annrheumdis-2018-214218
[47] Virzi F, Bianca P, Giammona A, et al. Combined platelet-rich plasma and lipofilling treatment provides great improvement in facial skin-induced lesion regeneration for scleroderma patients[J]. Stem Cell Res Ther, 2017, 8: 236. DOI: 10.1186/s13287-017-0690-3
[48] Serratrice N, Bruzzese L, Magalon J, et al. New fat-derived products for treating skin-induced lesions of scleroderma in nude mice[J]. Stem Cell Res Ther, 2014, 5: 138. DOI: 10.1186/scrt528
[49] Daumas A, Magalon J, Delaunay F, et al. Fat Grafting for Treatment of Facial Scleroderma[J]. Clin Plast Surg, 2020, 47: 155-163. DOI: 10.1016/j.cps.2019.08.016
[50] El Atat O, Antonios D, Hilal G, et al. An Evaluation of the Stemness, Paracrine, and Tumorigenic Characteristics of Highly Expanded, Minimally Passaged Adipose-Derived Stem Cells[J]. PLoS One, 2016, 11: e0162332. DOI: 10.1371/journal.pone.0162332
[51] Koh KS, Oh TS, Kim H, et al. Clinical application of human adipose tissue-derived mesenchymal stem cells in progressive hemifacial atrophy (Parry-Romberg disease) with microfat grafting techniques using 3-dimensional computed tomography and 3-dimensional camera[J]. Ann Plast Surg, 2012, 69: 331-337. DOI: 10.1097/SAP.0b013e31826239f0
[52] Tanikawa DY, Aguena M, Bueno DF, et al. Fat grafts supplemented with adipose-derived stromal cells in the rehabilitation of patients with craniofacial microsomia[J]. Plast Reconstr Surg, 2013, 132: 141-152.
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