Primed Mesenchymal Stem Cells Alter and Improve Rat Medial Collateral Ligament Healing.

Primed Mesenchymal Stem Cells Alter and Improve Rat Medial Collateral Ligament Healing.
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DOI:
10.1007/s12015-015-9633-5
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发表时间:
2016-02
影响因子:
4.8
通讯作者:
Vanderby R
Vanderby R
中科院分区:
医学3区
文献类型:
--
作者:
Saether EE;Chamberlain CS;Aktas E;Leiferman EM;Brickson SL;Vanderby R

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间充质干细胞(MSC)的细胞疗法可以改善组织愈合。然而,在植入前引发MSC可以进一步增强其治疗益处。然后进行该研究以测试引发MSC以更具抗炎性是否会增强大鼠韧带模型即内侧副韧带(MCL)中的愈合。使用浓度为1µg/ml的聚肌苷酸和聚胞苷酸(Poly(I:C))预处理MSC 48小时。手术横切大鼠MCL,并在损伤时给予1×106个细胞的载体溶液。在损伤后第4天和第14天,在接受引发的MSC、未引发的MSC或无细胞(对照)的韧带中分析一系列愈合指标。应用致敏的MSC通过影响内皮化、2型巨噬细胞存在、凋亡、前胶原1α和IL-1 Ra水平而有益地改变愈合。当分析MSC定位时,引发和未引发的MSC与内皮细胞和周细胞共定位,表明在血管生成中的支持作用。在植入前引发MSC改变了关键的韧带愈合事件,导致了更抗炎的环境,并改善了愈合。
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 hours using polyinosinic acid and polycytidylic acid (Poly (I:C)) at a concentration of 1µg/ml. Rat MCLs were surgically transected and administered 1×106 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.