Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration.

Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration.
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低氧预处理骨髓间充质干细胞促进成肌细胞融合和骨骼肌再生。

DOI:
10.1186/s13287-021-02530-3
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发表时间:
2021-08-09
影响因子:
7.5
通讯作者:
Brzoska E
Brzoska E
中科院分区:
医学2区
文献类型:
--
作者:
Archacka K;Grabowska I;Mierzejewski B;Graffstein J;Górzyńska A;Krawczyk M;Różycka AM;Kalaszczyńska I;Muras G;Stremińska W;Jańczyk-Ilach K;Walczak P;Janowski M;Ciemerych MA;Brzoska E

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骨骼肌的重建要归功于单能干细胞,即卫星细胞。卫星细胞处于静止状态,定位于肌纤维肌膜和基底膜之间。它们在肌肉损伤时被激活,增殖,分化为成肌细胞,并重建肌纤维。干细胞和祖细胞支持骨骼肌再生,而骨骼肌再生可能会受到广泛损伤、骨质疏松症、恶病质或营养不良等遗传病的干扰。许多证据表明,氧气水平调节细胞的增殖和分化过程。在本研究中,我们分析了低氧对人和猪骨髓间充质基质细胞(MSC)和小鼠成肌细胞增殖、分化和融合的影响。此外,还研究了低氧条件下培养的人骨髓间充质干细胞移植对骨骼肌再生的影响。我们发现在体外低氧条件下,骨髓间充质干细胞增加了血管内皮生长因子的表达,并促进了肌肉的生成。将低氧预适应的骨髓间充质干细胞移植到损伤肌肉中,可以改善细胞的植入和新血管的形成。提示低氧预适应骨髓间充质干细胞分泌的SDF-1和血管内皮生长因子在细胞植入和血管生成中起重要作用。重要的是,低氧预适应使骨髓来源的MSCs更有效地植入受损肌肉;然而,它们没有进行肌源性分化。网上版载有补充材料,可在10.1186/s13287-021-02530-3查阅。
The skeletal muscle reconstruction occurs thanks to unipotent stem cells, i.e., satellite cells. The satellite cells remain quiescent and localized between myofiber sarcolemma and basal lamina. They are activated in response to muscle injury, proliferate, differentiate into myoblasts, and recreate myofibers. The stem and progenitor cells support skeletal muscle regeneration, which could be disturbed by extensive damage, sarcopenia, cachexia, or genetic diseases like dystrophy. Many lines of evidence showed that the level of oxygen regulates the course of cell proliferation and differentiation. In the present study, we analyzed hypoxia impact on human and pig bone marrow-derived mesenchymal stromal cell (MSC) and mouse myoblast proliferation, differentiation, and fusion. Moreover, the influence of the transplantation of human bone marrow-derived MSCs cultured under hypoxic conditions on skeletal muscle regeneration was studied. We showed that bone marrow-derived MSCs increased VEGF expression and improved myogenesis under hypoxic conditions in vitro. Transplantation of hypoxia preconditioned bone marrow-derived MSCs into injured muscles resulted in the improved cell engraftment and formation of new vessels. We suggested that SDF-1 and VEGF secreted by hypoxia preconditioned bone marrow-derived MSCs played an essential role in cell engraftment and angiogenesis. Importantly, hypoxia preconditioned bone marrow-derived MSCs more efficiently engrafted injured muscles; however, they did not undergo myogenic differentiation. The online version contains supplementary material available at 10.1186/s13287-021-02530-3.
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