PDF(Pubmed)
Abstract：
UNASSIGNED: Morphea is a rare disease of unknown etiology without satisfactory treatment for skin sclerosis and soft tissue atrophy.
UNASSIGNED: To provide clinical, histologic, and transcriptome evidence of the antisclerotic and regenerative effects of sequential fat grafting with fresh fat and cryopreserved stromal vascular fraction gel (SVF gel) for morphea.
UNASSIGNED: This single-center, nonrandomized controlled trial was conducted between January 2022 and March 2023 in the Department of Plastic and Reconstructive Surgery of Nanfang Hospital, Southern Medical University and included adult participants with early-onset or late-onset morphea who presented with varying degrees of skin sclerosis and soft tissue defect.
UNASSIGNED: Group 1 received sequential grafting of fresh fat and cryopreserved SVF gel (at 1 and 2 months postoperation). Group 2 received single autologous fat grafting. All patients were included in a 12-month follow-up.
UNASSIGNED: The primary outcome included changes in the modified Localized Scleroderma Skin Severity Index (mLoSSI) and Localized Scleroderma Skin Damage Index (LoSDI) scores as evaluated by 2 independent blinded dermatologists. The histologic and transcriptome changes of morphea skin lesions were also evaluated.
UNASSIGNED: Of 44 patients (median [IQR] age, 26 [23-33] years; 36 women [81.8%]) enrolled, 24 (54.5%) were assigned to group 1 and 20 (45.5%) to group 2. No serious adverse events were noted. The mean (SD) mLoSSI scores at 12 months showed a 1.6 (1.50) decrease in group 1 and 0.9 (1.46) in group 2 (P = .13), whereas the mean (SD) LoSDI scores at 12 months showed a 4.3 (1.34) decrease in group 1 and 2.1 (1.07) in group 2 (P < .001), indicating that group 1 had more significant improvement in morphea skin damage but not disease activity compared with group 2. Histologic analysis showed improved skin regeneration and reduced skin sclerosis in group 1, whereas skin biopsy specimens of group 2 patients did not show significant change. Transcriptome analysis of skin biopsy specimens from group 1 patients suggested that tumor necrosis factor α signaling via NFκB might contribute to the immunosuppressive and antifibrotic effect of sequential fat grafting. A total of 15 hub genes were captured, among which many associated with morphea pathogenesis were downregulated and validated by immunohistochemistry, such as EDN1, PAI-1, and CTGF.
UNASSIGNED: The results of this nonrandomized trial suggest that sequential fat grafting with fresh fat and cryopreserved SVF gel was safe and its therapeutic effect was superior to that of single autologous fat grafting with improved mLoSSI and LoSDI scores. Histological and transcriptomic changes further support the effectiveness after treatment.
UNASSIGNED: Chinese Clinical Trial Registry identifier: ChiCTR2200058003.
UNASSIGNED: To provide clinical, histologic, and transcriptome evidence of the antisclerotic and regenerative effects of sequential fat grafting with fresh fat and cryopreserved stromal vascular fraction gel (SVF gel) for morphea.
UNASSIGNED: This single-center, nonrandomized controlled trial was conducted between January 2022 and March 2023 in the Department of Plastic and Reconstructive Surgery of Nanfang Hospital, Southern Medical University and included adult participants with early-onset or late-onset morphea who presented with varying degrees of skin sclerosis and soft tissue defect.
UNASSIGNED: Group 1 received sequential grafting of fresh fat and cryopreserved SVF gel (at 1 and 2 months postoperation). Group 2 received single autologous fat grafting. All patients were included in a 12-month follow-up.
UNASSIGNED: The primary outcome included changes in the modified Localized Scleroderma Skin Severity Index (mLoSSI) and Localized Scleroderma Skin Damage Index (LoSDI) scores as evaluated by 2 independent blinded dermatologists. The histologic and transcriptome changes of morphea skin lesions were also evaluated.
UNASSIGNED: Of 44 patients (median [IQR] age, 26 [23-33] years; 36 women [81.8%]) enrolled, 24 (54.5%) were assigned to group 1 and 20 (45.5%) to group 2. No serious adverse events were noted. The mean (SD) mLoSSI scores at 12 months showed a 1.6 (1.50) decrease in group 1 and 0.9 (1.46) in group 2 (P = .13), whereas the mean (SD) LoSDI scores at 12 months showed a 4.3 (1.34) decrease in group 1 and 2.1 (1.07) in group 2 (P < .001), indicating that group 1 had more significant improvement in morphea skin damage but not disease activity compared with group 2. Histologic analysis showed improved skin regeneration and reduced skin sclerosis in group 1, whereas skin biopsy specimens of group 2 patients did not show significant change. Transcriptome analysis of skin biopsy specimens from group 1 patients suggested that tumor necrosis factor α signaling via NFκB might contribute to the immunosuppressive and antifibrotic effect of sequential fat grafting. A total of 15 hub genes were captured, among which many associated with morphea pathogenesis were downregulated and validated by immunohistochemistry, such as EDN1, PAI-1, and CTGF.
UNASSIGNED: The results of this nonrandomized trial suggest that sequential fat grafting with fresh fat and cryopreserved SVF gel was safe and its therapeutic effect was superior to that of single autologous fat grafting with improved mLoSSI and LoSDI scores. Histological and transcriptomic changes further support the effectiveness after treatment.
UNASSIGNED: Chinese Clinical Trial Registry identifier: ChiCTR2200058003.
摘要：
■Morphea是一种病因不明的罕见疾病，对皮肤硬化和软组织萎缩没有满意的治疗方法。
■为了提供临床，组织学，和转录组证据表明，用新鲜脂肪和冷冻保存的基质血管部分凝胶（SVF凝胶）对硬叶进行顺序脂肪移植具有抗硬化和再生作用。
■这个单中心，非随机对照试验于2022年1月至2023年3月在南方医院整形外科进行，南方医科大学，包括患有早发型或晚发型的成年参与者，他们表现出不同程度的皮肤硬化和软组织缺损。
■第1组接受新鲜脂肪和冷冻保存的SVF凝胶的顺序移植（术后1和2个月）。第2组接受单次自体脂肪移植。所有患者均接受12个月的随访。
■主要结果包括由2名独立盲症皮肤科医生评估的改良的局部硬皮病皮肤严重程度指数（mLoSSI）和局部硬皮病皮肤损伤指数（LoSDI）评分的变化。还评估了硬头皮肤病变的组织学和转录组变化。
■44名患者（中位[IQR]年龄，26[23-33]岁；36名妇女[81.8%]）登记，24人（54.5%）被分配到第1组，20人（45.5%）被分配到第2组。未发现严重不良事件。12个月时的平均（SD）mLoSSI评分显示，第1组降低1.6（1.50），第2组降低0.9（1.46）（P=0.13），而12个月时的平均（SD）LoSDI评分显示，第1组降低4.3（1.34），第2组降低2.1（1.07）（P<.001），表明与第2组相比，第1组在硬叶皮肤损伤方面有更显著的改善，但没有疾病活动。组织学分析显示，第1组患者的皮肤再生改善，皮肤硬化减少，而第2组患者的皮肤活检标本没有显着变化。第1组患者皮肤活检标本的转录组分析表明，通过NFκB的肿瘤坏死因子α信号传导可能有助于序贯脂肪移植的免疫抑制和抗纤维化作用。总共捕获了15个hub基因，其中许多与硬伤发病机制相关的基因被下调，并通过免疫组织化学进行了验证，例如EDN1、PAI-1和CTGF。
■这项非随机试验的结果表明，新鲜脂肪和冷冻保存的SVF凝胶序贯脂肪移植是安全的，其治疗效果优于单一自体脂肪移植，mLoSSI和LoSDI评分得到改善。组织学和转录组变化进一步支持治疗后的有效性。
■中国临床试验注册中心标识符：ChiCTR2200058003。
■为了提供临床，组织学，和转录组证据表明，用新鲜脂肪和冷冻保存的基质血管部分凝胶（SVF凝胶）对硬叶进行顺序脂肪移植具有抗硬化和再生作用。
■这个单中心，非随机对照试验于2022年1月至2023年3月在南方医院整形外科进行，南方医科大学，包括患有早发型或晚发型的成年参与者，他们表现出不同程度的皮肤硬化和软组织缺损。
■第1组接受新鲜脂肪和冷冻保存的SVF凝胶的顺序移植（术后1和2个月）。第2组接受单次自体脂肪移植。所有患者均接受12个月的随访。
■主要结果包括由2名独立盲症皮肤科医生评估的改良的局部硬皮病皮肤严重程度指数（mLoSSI）和局部硬皮病皮肤损伤指数（LoSDI）评分的变化。还评估了硬头皮肤病变的组织学和转录组变化。
■44名患者（中位[IQR]年龄，26[23-33]岁；36名妇女[81.8%]）登记，24人（54.5%）被分配到第1组，20人（45.5%）被分配到第2组。未发现严重不良事件。12个月时的平均（SD）mLoSSI评分显示，第1组降低1.6（1.50），第2组降低0.9（1.46）（P=0.13），而12个月时的平均（SD）LoSDI评分显示，第1组降低4.3（1.34），第2组降低2.1（1.07）（P<.001），表明与第2组相比，第1组在硬叶皮肤损伤方面有更显著的改善，但没有疾病活动。组织学分析显示，第1组患者的皮肤再生改善，皮肤硬化减少，而第2组患者的皮肤活检标本没有显着变化。第1组患者皮肤活检标本的转录组分析表明，通过NFκB的肿瘤坏死因子α信号传导可能有助于序贯脂肪移植的免疫抑制和抗纤维化作用。总共捕获了15个hub基因，其中许多与硬伤发病机制相关的基因被下调，并通过免疫组织化学进行了验证，例如EDN1、PAI-1和CTGF。
■这项非随机试验的结果表明，新鲜脂肪和冷冻保存的SVF凝胶序贯脂肪移植是安全的，其治疗效果优于单一自体脂肪移植，mLoSSI和LoSDI评分得到改善。组织学和转录组变化进一步支持治疗后的有效性。
■中国临床试验注册中心标识符：ChiCTR2200058003。
