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An In Vitro Culture System That Supports Robust Expansion and Maintenance of In Vivo Engraftment Capabilities for Myogenic Progenitor Cells from Adult Mice

机译:体外培养系统,支持成年小鼠成肌祖细胞的稳健扩增和体内移植能力的维持

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Muscle cell therapy and tissue engineering require large numbers of functional muscle precursor/progenitor cells (MPCs), making the in vitro expansion of MPCs a critical step for these applications. The cells must maintain their myogenic properties upon robust expansion, especially for cellular therapy applications, in order to achieve efficacious treatment. A major obstacle associated with MPCs expansion is the loss of “stemness,” or regenerative capacity, of freshly isolated cells, presumably due to the absence of the native cellular niches. In the current study, we developed an in vitro system that allowed for long-term culture and massive expansion of murine MPCs (mMPCs) with the preservation of myogenic regeneration capabilities. Long term in vitro expanded mMPC expressed the myogenic stem cell markers Pax3 and Pax7 and formed spontaneously contracting myotubes. Furthermore, expanded mMPC injected into the tibialis anterior muscle of nude mice engrafted and formed myofibers. Collectively, the method developed in this study can be potentially adapted for the expansion of human MPCs to high enough numbers for treatment of muscle injuries in human patients.
机译:肌肉细胞治疗和组织工程需要大量的功能性肌肉前体/祖细胞(MPC),这使得MPC的体外扩增成为这些应用的关键步骤。为了获得有效的治疗,细胞必须在强大的扩增后保持其肌原性,特别是对于细胞治疗应用。与MPC扩增相关的主要障碍是新鲜分离细胞的“干性”或再生能力丧失,大概是由于天然细胞壁ni的缺乏。在当前的研究中,我们开发了一种体外系统,该系统可进行长期培养并允许鼠MPC(mMPC)的大规模扩增,同时保留成肌再生能力。长期体外扩增的mMPC表达了成肌干细胞标记Pax3和Pax7,并自发形成了收缩的肌管。此外,将扩展的mMPC注射到植入并形成肌纤维的裸鼠的胫骨前肌中。总体而言,本研究中开发的方法可以潜在地适用于将人MPC扩增到足够高的数量,以治疗人类患者的肌肉损伤。

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