周围神经损伤

    Mesenchymal stem cell treatment for peripheral nerve injury: a narrative review
  • Figure 1|Novel strategies using mesenchymal stem cells (MSCs) for curing peripheral nerve injury (PNI). 

    MSCs, a class of multipotent stem cells derived from the mesoderm, have been characterized as having high self-renewal ability, multi-directional differentiation potential and low immunogenicity. Because of their ubiquity, they can be easily isolated from various tissues such as bone marrow, umbilical cord and placenta (Pereira et al., 2018). Thus, they are often used as an ideal seed cell in cell therapy, with important clinical and research value. Great breakthroughs have been made using them in cardiovascular diseases, neurological diseases, autoimmune diseases and bone repair (Bartolucci et al., 2017; Chen et al., 2019). So far, MSCs have been combined with biological tissue engineering using various techniques to improve the effect of PNI regeneration and repair, but each application method has certain advantages and disadvantages. Therefore, the optimal method for MSCs to repair PNI needs further exploration. This review assesses the various techniques of MSCs for PNI (Figure 1) and provides a scientific basis for the direction of future research.


    Figure 2|Neurons regenerate after peripheral nerve injuries.

    Neurons in the peripheral nerve system can regenerate even after a severe PNI, but the potential for healing after accessible surgical therapy is dependent upon the brain as well as factors distal to the injury (Fex Svennigsen and Dahlin, 2013). Cortical plasticity has been identified as a contributary factor in the rehabilitation for patients with PNI (Baldassarre et al., 2020). Adult PNI patients may never achieve an encouraging outcome of functional recovery. This is because the brain is unable to accept the new afferent signaling patterns from the periphery caused by misdirection of the axonal regeneration after nerve injury. However, children show an admirable clinical recovery after PNIs, which may be because of the better regeneration and greater plasticity of the young brain (Chemnitz et al., 2013). At the time axons regenerate, the SCs have begun to proliferate, migrate and line up in nerves, which creates bands of Büngner and offers guidance substrates for the re-growth of axons (Bunn et al., 2019). SCs, specific type of cells that wrap around the axon of neurons in the peripheral nerve system, may play a vital role in the regeneration of axons (Gordon, 2020). The SCs in the bands of Büngner could produce an array of growth promoting factors, such as glial derived neurotrophic factor, ciliary neurotrophic factor, insulin like growth factor-1 and neuroregulin 1 (NRG1) (Springer et al., 1994; Tonazzini et al., 2017; Zhu et al., 2018; Godinho et al., 2020; Figure 2). PNI is followed by responses from the surrounding neural and non-neural cells, both proximally and distally to the damaged area. The endogenous repair process in neurons starts with an increase in its cell body size, the Nissl bodies dissolve and initiate a process of protein synthesis (Perrin et al., 2005). Then fragmentation of the axon is mediated by activated intrinsic proteases, including the ubiquitin-protease system and calpain (Zhai et al., 2003). Axonal and myelin debris is later phagocytosed by SCs and recruited macrophages that, attracted by specific chemokines, infiltrate through the myelin sheathing and broken blood-nerve-barrier (Coleman and Freeman, 2010; Figure 2). Clearance of myelin debris is a critical step for repair since myelin contains inhibitors of axonal regeneration (Berghoff et al., 2020). It is known that some adhesion proteins and growth factors affect axonal growth, Schwann cell proliferation and the formation of Büngner bands. Thus, understanding which proteins are critical in promoting the re-growth process will be useful for the improvements in peripheral nerve surgery and in the development to bridge nerve defects. It has been indicated that NRG1, probably along with laminin, is responsible for Schwann cell migration in nerve regeneration (Chang et al., 2013; Heermann and Schwab, 2013). The presence of laminin is also critical in the outgrowth of axons, and is now used clinically to reconstruct nerve defects (Kvist et al., 2011). Although axon regeneration and remyelination occur in the peripheral nerve system, the remyelinated axons often have a decreased internodal length and thinner myelin sheaths, which causes slower conduction (Sherman and Brophy, 2005). This is not only observed in the repair of acute nerve injury but is also observed after decompression of the median nerve in carpal tunnel syndrome and nerve repair in human median and ulnar nerves (Kim et al., 2000). These undesirable results might be due to either insufficient stimulation of redifferentiated SCs or inhibitory signals (Sherman and Brophy, 2005). Because of the unsatisfactory regaining of function, further improvements in PNI repair and regeneration have become an area of much interest.


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  • 发布日期: 2021-04-20  浏览: 568
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