Saether Erin E, Chamberlain Connie S, Aktas Erdem, Leiferman Ellen M, Brickson Stacey L, Vanderby Ray
Department of Biomedical Engineering, University of Wisconsin, 1111 Highland Ave, WIMR Room 5059, Madison, WI, 53705, USA.
Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI, 53705, USA.
Stem Cell Rev Rep. 2016 Feb;12(1):42-53. doi: 10.1007/s12015-015-9633-5.
Cell therapy with mesenchymal stem cells (MSCs) can improve tissue healing. It is possible, however, that priming MSCs prior to implantation can further enhance their therapeutic benefit. This study was then performed to test whether priming MSCs to be more anti-inflammatory would enhance healing in a rat ligament model, i.e. a medial collateral ligament (MCL). MSCs were primed for 48 h using polyinosinic acid and polycytidylic acid (Poly (I:C)) at a concentration of 1 μg/ml. Rat MCLs were surgically transected and administered 1 × 10(6) cells in a carrier solution at the time of injury. A series of healing metrics were analyzed at days 4 and 14 post-injury in the ligaments that received primed MSCs, unprimed MSCs, or no cells (controls). Applying primed MSCs beneficially altered healing by affecting endothelialization, type 2 macrophage presence, apoptosis, procollagen 1α, and IL-1Ra levels. When analyzing MSC localization, both primed and unprimed MSCs co-localized with endothelial cells and pericytes suggesting a supportive role in angiogenesis. Priming MSCs prior to implantation altered key ligament healing events, resulted in a more anti-inflammatory environment, and improved healing.
间充质干细胞（MSCs）的细胞疗法可促进组织愈合。然而，在植入前对MSCs进行预处理可能会进一步增强其治疗效果。因此，本研究旨在测试将MSCs预处理为更具抗炎性是否会增强大鼠韧带模型（即内侧副韧带，MCL）的愈合。使用浓度为1μg/ml的聚肌苷酸和聚胞苷酸（Poly（I:C））对MSCs进行48小时预处理。手术切断大鼠MCL，并在损伤时在载体溶液中给予1×10(6)个细胞。在损伤后第4天和第14天，对接受预处理的MSCs、未预处理的MSCs或无细胞（对照）的韧带中的一系列愈合指标进行分析。应用预处理的MSCs通过影响内皮化、2型巨噬细胞的存在、细胞凋亡、原胶原1α和IL-1Ra水平，有益地改变了愈合。在分析MSCs的定位时，预处理和未预处理的MSCs均与内皮细胞和周细胞共定位，表明在血管生成中起支持作用。在植入前对MSCs进行预处理可改变关键的韧带愈合事件，形成更具抗炎性的环境，并改善愈合。
