Volumetric muscle loss injury repair using in situ fibrin gel cast seeded with muscle-derived stem cells (MDSCs).

Volumetric muscle loss injury repair using in situ fibrin gel cast seeded with muscle-derived stem cells (MDSCs).
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DOI:
10.1016/j.scr.2018.01.008
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发表时间:
2018-03
期刊:
影响因子:
1.2
通讯作者:
Darabi R
Darabi R
中科院分区:
医学4区
文献类型:
--
作者:
Matthias N;Hunt SD;Wu J;Lo J;Smith Callahan LA;Li Y;Huard J;Darabi R

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由创伤或战斗损伤引起的肌肉体积缺陷是导致严重发病率的主要健康问题。其特征在于肌肉及其生物支架的部分或全部厚度损失,导致广泛的纤维化和瘢痕形成。因此,理想的治疗选择是使用干细胞结合生物支架来恢复肌肉。肌源性干细胞(muscle-derived stem cells,MDSC)因其独特的多向分化潜能而成为一个很好的候选细胞。在这项研究中,我们评估了再生潜力的MDSCs肌肉损失修复使用一种新的原位纤维蛋白凝胶铸造。通过在NSG小鼠的胫骨前肌(TA)中进行部分厚度楔形切除来产生肌肉缺损,其产生平均25%的质量损失。如果不治疗,这种缺陷会导致严重的肌肉纤维化。接下来,使用新的原位纤维蛋白凝胶浇铸方法递送MDSC。我们的研究结果表明,MDSCs能够植入并形成新的肌纤维缺损时,铸造与纤维蛋白凝胶沿着。LacZ标记的MDSC能够有效地分化为新的肌纤维并显著增加肌肉质量。这也伴随着移植肌肉中纤维化组织的显著减少。此外,移植的细胞也有助于新血管形成和卫星细胞种植。这些结果证实了MDSC的治疗潜力和纤维蛋白/MDSC混合物直接原位浇铸修复肌肉质量缺损的可行性。
Volumetric muscle defect, caused by trauma or combat injuries, is a major health concern leading to severe morbidity. It is characterized by partial or full thickness loss of muscle and its bio-scaffold, resulting in extensive fibrosis and scar formation. Therefore, the ideal therapeutic option is to use stem cells combined with bio-scaffolds to restore muscle. For this purpose, muscle-derived stem cells (MDSCs) are a great candidate due to their unique multi-lineage differentiation potential. In this study, we evaluated the regeneration potential of MDSCs for muscle loss repair using a novel in situ fibrin gel casting. Muscle defect was created by a partial thickness wedge resection in the tibialis anterior (TA)muscles of NSG mice which created an average of 25% mass loss. If untreated, this defect leads to severe muscle fibrosis. Next, MDSCs were delivered using a novel in situ fibrin gel casting method. Our results demonstrated MDSCs are able to engraft and form new myofibers in the defect when casted along with fibrin gel. LacZ labeled MDSCs were able to differentiate efficiently into new myofibers and significantly increase muscle mass. This was also accompanied by significant reduction of fibrotic tissue in the engrafted muscles. Furthermore, transplanted cells also contributed to new vessel formation and satellite cell seeding. These results confirmed the therapeutic potential of MDSCs and feasibility of direct in situ casting of fibrin/MDSC mixture to repair muscle mass defects.
DOI: 10.1083/jcb.200108150
发表时间: 2002-05-27
期刊: The Journal of cell biology
影响因子: --
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