Muscle acellular scaffold as a biomaterial: effects on C2C12 cell differentiation and interaction with the murine host environment.

Muscle acellular scaffold as a biomaterial: effects on C2C12 cell differentiation and interaction with the murine host environment.
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DOI:
10.3389/fphys.2014.00354
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发表时间:
2014
影响因子:
4
通讯作者:
Tatullo M
Tatullo M
中科院分区:
医学2区
文献类型:
--
作者:
Perniconi B;Coletti D;Aulino P;Costa A;Aprile P;Santacroce L;Chiaravalloti E;Coquelin L;Chevallier N;Teodori L;Adamo S;Marrelli M;Tatullo M

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脱细胞器官的细胞外基质(ECM)具有理想的组织工程支架的特性(即组织相容性、多孔性、可降解性、无毒性)。我们先前观察到肌肉去细胞支架(MAS)在体内是一个促进肌原的环境。为了确定MAS(基本上是肌肉ECM)是否表现为肌源性环境,无论其位置如何,我们分析了MAS与肌肉和非肌肉细胞和组织的相互作用,以评估MAS对细胞分化的影响。骨形态发生蛋白处理MAS内培养的C2C12细胞在体外诱导成骨分化,从而提示MAS并不不可逆转地将细胞定向成肌。在体内,当替换肌肉时,MAS支持新生肌肉纤维的形成(原位)。然而,当移植到肾被膜内时,异位移植的大脑中动脉并没有产生肌纤维。此外,尽管存在大量沿层粘连蛋白的MAS结构迁移的细胞,但在剑突下移植MAS时,没有观察到肌肉形成。综上所述,我们的结果表明,MAS本身不足以诱导肌源性分化。MAS的促肌生环境很可能与肌肉支架的固有属性(如特定的肌肉ECM蛋白)没有严格的关系。事实上,更有可能的是,肌源性干细胞定植于大脑中动脉,识别肌肉环境,最终允许肌源性终末分化。总之,MAS可能代表了肌肉和非肌肉3D结构的合适环境,其特征是高度组织化的结构,其相对稳定性促进了与周围组织的整合。我们的工作强调了MAS的可塑性,这表明MAS可能被考虑用于更广泛的组织工程应用,而不仅仅是替代体积肌肉丢失。
The extracellular matrix (ECM) of decellularized organs possesses the characteristics of the ideal tissue-engineering scaffold (i.e., histocompatibility, porosity, degradability, non-toxicity). We previously observed that the muscle acellular scaffold (MAS) is a pro-myogenic environment in vivo. In order to determine whether MAS, which is basically muscle ECM, behaves as a myogenic environment, regardless of its location, we analyzed MAS interaction with both muscle and non-muscle cells and tissues, to assess the effects of MAS on cell differentiation. Bone morphogenetic protein treatment of C2C12 cells cultured within MAS induced osteogenic differentiation in vitro, thus suggesting that MAS does not irreversibly commit cells to myogenesis. In vivo MAS supported formation of nascent muscle fibers when replacing a muscle (orthotopic position). However, heterotopically grafted MAS did not give rise to muscle fibers when transplanted within the renal capsule. Also, no muscle formation was observed when MAS was transplanted under the xiphoid process, in spite of the abundant presence of cells migrating along the laminin-based MAS structure. Taken together, our results suggest that MAS itself is not sufficient to induce myogenic differentiation. It is likely that the pro-myogenic environment of MAS is not strictly related to the intrinsic properties of the muscle scaffold (e.g., specific muscle ECM proteins). Indeed, it is more likely that myogenic stem cells colonizing MAS recognize a muscle environment that ultimately allows terminal myogenic differentiation. In conclusion, MAS may represent a suitable environment for muscle and non-muscle 3D constructs characterized by a highly organized structure whose relative stability promotes integration with the surrounding tissues. Our work highlights the plasticity of MAS, suggesting that it may be possible to consider MAS for a wider range of tissue engineering applications than the mere replacement of volumetric muscle loss.
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