New fat-derived products for treating skin-induced lesions of scleroderma in nude mice

Abstract

IntroductionScleroderma is characterized by cutaneous manifestations that mainly affect the hands, arms and face. As of today, there is no treatment for fibrotic skin lesions of scleroderma. Previously we generated and validated a model of scleroderma-like skin sclerosis in nude mice, appropriate to inject human derived products. We showed that the subcutaneous injection of micro-fat (MF), purified and injected using small caliber cannulas, have anti-fibrotic and pro-angiogenic effects and appears more suitable for the treatment of skin lesions of scleroderma compared to the gold standard (Coleman’s technique or macro-fat). Here we compared the long-term efficacy of micro-fat “enriched” with other therapeutic products including the stromal vascular fraction (SVF) of fat and platelet-rich plasma (PRP) from blood in our murine model of scleroderma.MethodsWe used 72 nude mice in this study. We formed six experimental groups: Macro-fat, MF, SVF, PRP, MF + SVF, MF + PRP. This project has three phases: i) Induction of skin sclerosis by daily subcutaneous injections of bleomycin (BLM) for 4 weeks in nude mice; ii) Purification and injection of the different cell therapy products; iii) Histological analyses done 8 weeks post-injections.ResultsMF + SVF and MF + PRP significantly reversed dermal and epidermal sclerosis (P <0.01). Macro-fat, SVF, PRP only corrected the dermal sclerosis (P <0.05). Epidermal sclerosis was reduced in treatments containing MF (P <0.01). MF was more stable. Products containing the SVF were associated with a significant increase of the local vascularization (P <0.01).ConclusionsAll tested substances were effective in treating skin-induced lesions of scleroderma with different levels of fibrosis and vascular improvement; MF derived products are more stable and SVF demonstrated better pro-angiogenic effects. The observed efficacy of this combination of products in the animal model provides a rationale for potential clinical applications to treat human disease.

Molecular profile and proangiogenic activity of the adipose-derived stromal vascular fraction used as an autologous innovative medicinal product in patients with systemic sclerosis

“…Changes in secondary endpoints indicated potential efficacy in the improvement of Raynaud’s phenomenon, digital ulcers, hand pain and global quality of life at 6 and 24 months compared with baseline 19 20. The predominant improvement of peripheral vascular manifestations was consistent with the beneficial proangiogenic effects of SVF reported in experimental models and emerging clinical trials addressing ischaemic diseases 21–23. However, alterations of the progenitor cell-dependent endogenous capacity for vascular repair are involved in the SSc pathogenesis,24 25 which raises questions about the therapeutic potency of autologous SVF in this disease.…”

Combined platelet-rich plasma and lipofilling treatment provides great improvement in facial skin-induced lesion regeneration for scleroderma patients

“…SSc patients show a high production of VEGF, which is not however followed by an improvement of endothelial capillarity, giving rise to telangiectasia [ 28 , 29 ]. Being that a single lipofilling treatment usually is not sufficient in order to obtain efficient regeneration in SSc patients, a combination of autologous tissue together with an abundant cytokine source would be preferable [ 30 – 33 ].…”

First clinical case report of local microinjection of autologous fat and adipose-derived stromal vascular fraction for perianal fistula in Crohn’s disease

“…In fact, we obtained promising effects with complete clinical and radiological healing of the fistula without any secondary effects. Although the mechanism of action of ADSVF remains poorly understood, findings from prior preclinical and clinical studies in various fields suggest that the combination of angiogenic and anti-inflammatory effects of ADSVF [ 13 , 14 ] is primarily attributable to the high proportion of MSCs and endothelial progenitor cells; in the reported case, these two types of cells accounted for 38.6% and 4.3%, respectively, of the 22.8 million injected cells. The synergistic effects of these two cell subsets in tissue regeneration and neovascularization have previously been described [ 15 ].…”