Autologous Fractionated Adipose Tissue as a Natural Biomaterial and Novel One-Step Stem Cell Therapy for Repairing Articular Cartilage Defects
Autologous Fractionated Adipose Tissue as a Natural Biomaterial and Novel One-Step Stem Cell Therapy for Repairing Articular Cartilage Defects
复制标题
自体分馏脂肪组织作为一种天然生物材料和用于修复关节软骨缺损的新型一步干细胞疗法
DOI：
10.3389/fcell.2020.00694
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发表时间：
2020-07-31
影响因子：
5.5
通讯作者：
Ao, Yingfang
中科院分区：
文献类型：
--
作者：
Li, Qi;Zhao, Fengyuan;Ao, Yingfang
关节软骨损伤仍然是临床医生面临的一个坚韧挑战。干细胞已成为再生医学中有前途的生物制剂。以往的研究已经广泛证明，脂肪间充质干细胞（ADSCs）可以促进软骨修复，由于其多能性。然而，脂肪干细胞的酶分离和单层扩增降低了其分化潜能，限制了其临床应用。本研究通过简单的机械移位和离心分离脂肪油并浓缩有效成分，获得了一种新型的脂肪组织衍生产品，细胞外基质/基质血管组分凝胶（ECM/SVF-gel）。本研究旨在评价这种天然生物材料对关节软骨缺损修复的治疗效果。扫描电子显微镜显示ECM/SVF-凝胶中的纤维结构被保留。从ECM/SVF-凝胶中萌发的ADSC的特征在于其分化为软骨细胞、成骨细胞和脂肪细胞的能力。在兔模型中，产生临界尺寸的软骨缺损（直径，4 mm;深度，1.5mm），并用微骨折（MF）或自体ECM/SVF-凝胶注射的组合进行治疗。在6周和12周时通过磁共振成像、宏观观察、组织学和免疫组织化学对膝关节进行评估。ECM/SVF凝胶组的国际腕关节修复学会评分和组织学评分显著高于MF治疗组。与单独的MF治疗相比，ECM/SVF-凝胶明显改善了软骨再生、与周围正常软骨的整合以及透明软骨标志物II型胶原的表达。总的来说，即用型ECM/SVF凝胶是一种有前途的促进关节软骨再生的治疗策略。此外，由于简单，省时，成本效益，无酶和微创制备过程，这种凝胶提供了一个有价值的替代干细胞为基础的治疗临床翻译。
Articular cartilage damage remains a tough challenge for clinicians. Stem cells have emerged promising biologics in regenerative medicine. Previous research has widely demonstrated that adipose-derived mesenchymal stem cells (ADSCs) can promote cartilage repair due to their multipotency. However, enzymatic isolation and monolayer expansion of ADSCs decrease their differentiation potential and limit their clinical application. Here, a novel adipose tissue-derived product, extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel), was obtained by simple mechanical shifting and centrifugation to separate the fat oil and concentrate the effective constituents. This study aimed to evaluate the therapeutic effect of this natural biomaterial on the repair of articular cartilage defects. Scanning electron microscopy showed that the fibrous structure in the ECM/SVF-gel was preserved. ADSCs sprouted from the ECM/SVF-gel were characterized by their ability of differentiation into chondrocytes, osteoblasts, and adipocytes. In a rabbit model, critical-sized cartilage defects (diameter, 4 mm; depth, 1.5 mm) were created and treated with microfracture (MF) or a combination of autologous ECM/SVF-gel injection. The knee joints were evaluated at 6 and 12 weeks through magnetic resonance imaging, macroscopic observation, histology, and immunohistochemistry. The International Cartilage Repair Society score and histological score were significantly higher in the ECM/SVF-gel group than those in the MF-treated group. The ECM/SVF-gel distinctly improved cartilage regeneration, integration with surrounding normal cartilage, and the expression of hyaline cartilage marker, type II collagen, in comparison with the MF treatment alone. Overall, the ready-to-use ECM/SVF-gel is a promising therapeutic strategy to facilitate articular cartilage regeneration. Moreover, due to the simple, time-sparing, cost-effective, enzyme-free, and minimally invasive preparation process, this gel provides a valuable alternative to stem cell-based therapy for clinical translation.