ter Huurne Menno, Schelbergen Rik, Blattes Roxane, Blom Arjen, de Munter Wouter, Grevers Lilyanne C, Jeanson Jannik, Noël Danièle, Casteilla Louis, Jorgensen Christian, van den Berg Wim, van Lent Peter L E M
Radboud University Nijmegen Medical Centre, The Netherlands.
Arthritis Rheum. 2012 Nov;64(11):3604-13. doi: 10.1002/art.34626.
In experimental collagenase-induced osteoarthritis (OA) in the mouse, synovial lining macrophages are crucial in mediating joint destruction. It was recently shown that adipose-derived stem cells (ASCs) express immunosuppressive characteristics. This study was undertaken to explore the effect of intraarticular injection of ASCs on synovial lining thickness and its relation to joint pathology in experimental mouse OA.
ASCs were isolated from fat surrounding the inguinal lymph nodes and cultured for 2 weeks. Experimental OA was induced by injection of collagenase into the knee joints of C57BL/6 mice. OA phenotypes were measured within 8 weeks after induction. Histologic analysis was performed, and synovial thickening, enthesophyte formation, and cartilage destruction were measured in the knee joint.
ASCs were injected into the knee joints of mice 7 days after the induction of collagenase-induced OA. On day 1, green fluorescent protein-labeled ASCs were attached to the lining layer in close contact with macrophages. Thickening of the synovial lining, formation of enthesophytes associated with medial collateral ligaments, and formation of enthesophytes associated with cruciate ligaments were significantly inhibited on day 42 after ASC treatment, by 31%, 89%, and 44%, respectively. Destruction of cartilage was inhibited on day 14 (65%) and day 42 (35%). In contrast to early treatment, injection of ASCs on day 14 after OA induction showed no significant effect on synovial activation or joint pathology on day 42.
These findings indicate that a single injection of ASCs into the knee joints of mice with early-stage collagenase-induced OA inhibits synovial thickening, formation of enthesophytes associated with ligaments, and cartilage destruction.
在实验性胶原酶诱导的小鼠骨关节炎（OA）中，滑膜衬里巨噬细胞在介导关节破坏中起关键作用。最近研究表明，脂肪来源干细胞（ASC）具有免疫抑制特性。本研究旨在探讨关节内注射ASC对实验性小鼠OA滑膜衬里厚度的影响及其与关节病理的关系。
从腹股沟淋巴结周围脂肪中分离ASC并培养2周。通过向C57BL/6小鼠膝关节注射胶原酶诱导实验性OA。在诱导后8周内测量OA表型。进行组织学分析，并测量膝关节滑膜增厚、韧带附着点骨赘形成和软骨破坏情况。
在胶原酶诱导的OA诱导7天后，将ASC注射到小鼠膝关节。第1天，绿色荧光蛋白标记的ASC附着于衬里层，与巨噬细胞紧密接触。在ASC治疗后第42天，滑膜衬里增厚、与内侧副韧带相关的韧带附着点骨赘形成以及与十字韧带相关的韧带附着点骨赘形成分别显著受到抑制，抑制率分别为31%、89%和44%。软骨破坏在第14天（65%）和第42天（35%）受到抑制。与早期治疗相比，OA诱导后第14天注射ASC对第42天的滑膜激活或关节病理无显著影响。
这些发现表明，单次向早期胶原酶诱导的OA小鼠膝关节注射ASC可抑制滑膜增厚、与韧带相关的韧带附着点骨赘形成以及软骨破坏。
