New fat-derived products for treating skin-induced lesions of scleroderma in nude mice.
New fat-derived products for treating skin-induced lesions of scleroderma in nude mice.
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DOI：
10.1186/scrt528
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发表时间：
2014-12-17
影响因子：
7.5
通讯作者：
Magalon G
中科院分区：
文献类型：
--
作者：
Serratrice N;Bruzzese L;Magalon J;Véran J;Giraudo L;Aboudou H;Ould-Ali D;Nguyen PS;Bausset O;Daumas A;Casanova D;Granel B;Andrac-Meyer L;Sabatier F;Magalon G
硬皮病的特征是皮肤表现，主要影响手，手臂和面部。到目前为止，还没有治疗硬皮病的纤维化皮肤病变的方法。之前，我们在裸鼠中生成并验证了硬皮病样皮肤硬化模型，该模型适合于注射人源性产品。我们表明，皮下注射的微脂肪（MF），纯化和注射使用小口径套管，具有抗纤维化和促血管生成的作用，似乎更适合硬皮病的皮肤病变的治疗相比，金标准（科尔曼的技术或宏脂肪）。在这里，我们比较了微脂肪“富集”与其他治疗产品的长期疗效，包括脂肪的基质血管成分（SVF）和来自硬皮病小鼠模型血液的富血小板血浆（PRP）。我们在这项研究中使用了72只裸鼠。实验分为6个实验组：粗脂肪组、MF组、SVF组、PRP组、MF + SVF组、MF + PRP组。该项目分为三个阶段：i）在裸鼠中通过每天皮下注射博来霉素（BLM）持续4周诱导皮肤硬化; ii）纯化和注射不同的细胞治疗产品; iii）注射后8周进行组织学分析。MF + SVF和MF + PRP可明显逆转真皮和表皮硬化（P <0.01）。巨脂、SVF、PRP仅能纠正皮肤硬化（P <0.05）。含MF的治疗组的表皮硬化减少（P <0.01）。MF更稳定。含有SVF的产品与局部血管化显著增加相关（P <0.01）。所有测试物质均有效治疗硬皮病的皮肤诱导的病变，具有不同水平的纤维化和血管改善; MF衍生产品更稳定，SVF表现出更好的促血管生成作用。在动物模型中观察到的这种产品组合的疗效为治疗人类疾病的潜在临床应用提供了依据。
Scleroderma 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. We 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. MF + 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). All 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.
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影响因子：
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