Clinical, Histologic, and Transcriptomic Evaluation of Sequential Fat Grafting for Morphea

SDCC 

Morphea, also called localized scleroderma (LoS), is a rare disease of unknown etiology without satisfactory treatment for skin sclerosis and soft tissue atrophy. To provide clinical, histologic, and transcriptome evidence of the anti-sclerotic and regenerative effects of sequential fat grafting with fresh fat and cryopreserved stromal vascular fraction-gel (SVF-gel) for LoS. We conducted this single-center, non-randomized controlled trial between January 2022 and March 2023. This study was conducted in the Department of Plastic and Reconstructive Surgery of Nanfang Hospital, Southern Medical University. Adult participants with young or old-onset LoS, and presented with varying degrees of skin sclerosis and soft tissue defect. Group A received sequential grafting of fresh fat and cryopreserved SVF-gel (at 1 and 2 months post-operation). Group B received single autologous fat grafting. All patients were included in a 12-month follow-up. The primary outcome included changes in the modified Localized Scleroderma Skin Severity Index (mLoSSI) and Localized Scleroderma Skin Damage Index (LoSDI) scores evaluated by two independent blinded dermatologists. The histologic and transcriptome changes of LoS skin lesions were also evaluated. Of 44 patients (median [IQR] age, 26 [23-33] years) enrolled, 24 were assigned to Group A and 20 to Group B. No serious adverse events were noted. The mean mLoSSI scores at 12 months showed a 1.6 (SD [standard deviation], 1.50) decrease in Group A and 0.9 (SD, 1.46) in Group B (p=.134), whereas the mean LoSDI scores at 12 months showed a 4.3 (SD, 1.34) decrease in Group A and 2.1 (SD, 1.07) in Group B (p<.001), indicating that Group A had a more significant effect in reversing LoS skin damage but not disease activity compared with Group B. Histologic analysis showed improved skin regeneration and reduced skin sclerosis in Group A, whereas skin biopsies of Group B patients did not show significant change. Transcriptome analysis of skin biopsies from Group A patients suggested "TNFα signaling via NF-κB" might be at central play in the immunosuppressive and anti-fibrotic effect of sequential fat grafting. 15 hub genes were captured, among which many associated with scleroderma pathogenesis were down-regulated and validated by immunohistochemistry, such as EDN1, PAI-1, and CTGF. Sequential fat grafting with fresh fat and cryopreserved SVF-gel was safe and its therapeutic effect is superior to that of single autologous fat transplantation with improved mLoSSI and LoSDI scores. Histological and transcriptomic changes further support the effective changes after treatment.

Craniomaxillofacial/Head and Neck

PSTM 2024