Therapeutic assessment of mesenchymal stem cells delivered within a PEGylated fibrin gel following an ischemic injury.
Therapeutic assessment of mesenchymal stem cells delivered within a PEGylated fibrin gel following an ischemic injury.
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DOI：
10.1016/j.biomaterials.2016.06.011
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发表时间：
2016-09
期刊：
影响因子：
14
通讯作者：
Suggs LJ
中科院分区：
文献类型：
--
作者：
Ricles LM;Hsieh PL;Dana N;Rybalko V;Kraynak C;Farrar RP;Suggs LJ
当前研究的目的是研究MSC对缺血组织血管再生和功能恢复的治疗贡献。我们使用了啮齿动物后肢缺血模型，并在肌肉内传递了卵纤维蛋白凝胶基质中的MSC。在该模型中，我们证明了MSC治疗在卵纤维纤维蛋白中递送时，会导致成熟的血管形成明显更高，从而使骨骼肌组织的功能恢复更大，如使用力生产测量评估。我们观察到在没有类纤维纤维蛋白的情况下提供MSC的早期时间点的初始迹象，但这并没有长期持续或导致组织的恢复。此外，单独用纤维化纤维蛋白治疗的动物表现出更多的成熟血管，但它们没有动脉化，也没有显示出武力产生的改善。这些结果表明，缺血性组织的血运重建可能是完成受伤组织的功能修复的必要步骤。这项工作对缺血性疾病的干细胞疗法具有影响，也有可能在评估此类疗法的情况下。
The intent of the current study was to investigate the therapeutic contribution of MSCs to vascular regeneration and functional recovery of ischemic tissue. We used a rodent hind limb ischemia model and intramuscularly delivered MSCs within a PEGylated fibrin gel matrix. Within this model, we demonstrated that MSC therapy, when delivered in PEGylated fibrin, results in significantly higher mature blood vessel formation, which allows for greater functional recovery of skeletal muscle tissue as assessed using force production measurements. We observed initial signs of vascular repair at early time points when MSCs were delivered without PEGylated fibrin, but this did not persist or lead to recovery of the tissue in the long-term. Furthermore, animals which were treated with PEGylated fibrin alone exhibited a greater number of mature blood vessels, but they did not arterialize and did not show improvements in force production. These results demonstrate that revascularization of ischemic tissue may be a necessary but not sufficient step to complete functional repair of the injured tissue. This work has implications on stem cell therapies for ischemic diseases and also potentially on how such therapies are evaluated.