Cartilage Biology and Orthopaedic Branch, Department of Health and Human Services, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health, Bethesda, MD MSC 8022, USA.
Mol Biotechnol. 2012 Jun;51(2):128-36. doi: 10.1007/s12033-011-9445-z.
Peripheral nerve damage frequently accompanies musculoskeletal trauma and repair of these nerves could be enhanced by the targeted application of neurotrophic factors (NTFs), which are typically expressed by endogenous cells that support nerve regeneration. Injured muscle tissues express NTFs to promote reinnervation as the tissue regenerates, but the source of these factors from within the muscles is not fully understood. We have previously identified a population of mesenchymal progenitor cells (MPCs) in traumatized muscle tissue with properties that support tissue regeneration, and our hypothesis was that MPCs also secrete the NTFs that are associated with muscle tissue reinnervation. We determined that MPCs express genes associated with neurogenic function and measured the protein-level expression of specific NTFs with known functions to support nerve regeneration. We also demonstrated the effectiveness of a neurotrophic induction protocol to enhance the expression of the NTFs, which suggests that the expression of these factors may be modulated by the cellular environment. Finally, neurotrophic induction affected the expression of cell surface markers and proliferation rate of the MPCs. Our findings indicate that traumatized muscle-derived MPCs may be useful as a therapeutic cell type to enhance peripheral nerve regeneration following musculoskeletal injury.
周围神经损伤常伴有肌肉骨骼创伤,通过神经营养因子(NTFs)的靶向应用可以增强这些神经的修复,NTFs 通常由支持神经再生的内源性细胞表达。受伤的肌肉组织表达 NTFs 以促进神经再支配,因为组织在再生,但这些因素的来源在肌肉内尚不完全清楚。我们之前在受伤的肌肉组织中发现了一群具有支持组织再生特性的间充质祖细胞(MPCs),我们的假设是 MPCs 也分泌与肌肉组织神经再支配相关的 NTFs。我们确定 MPCs 表达与神经发生功能相关的基因,并测量特定 NTFs 的蛋白水平表达,这些 NTFs 具有已知的支持神经再生的功能。我们还证明了神经营养诱导方案可以增强 NTFs 的表达,这表明这些因子的表达可能受到细胞环境的调节。最后,神经营养诱导影响 MPCs 的表面标记物表达和增殖率。我们的研究结果表明,受伤的肌肉来源的 MPCs 可能是一种有用的治疗细胞类型,可以增强肌肉骨骼损伤后周围神经的再生。