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A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury

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Title: A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury
Authors: Endo, Takeshi Browse this author
Kadoya, Ken Browse this author →KAKEN DB
Suzuki, Yuki Browse this author
Kawamura, Daisuke Browse this author →KAKEN DB
Iwasaki, Norimasa Browse this author →KAKEN DB
Keywords: peripheral nerve injury
axon regeneration
experimental model
Schwann cell
bone marrow stromal cell
Issue Date: 28-Jun-2019
Publisher: Frontiers Media
Journal Title: Frontiers in cellular neuroscience
Volume: 13
Start Page: 280
Publisher DOI: 10.3389/fncel.2019.00280
PMID: 31316351
Abstract: Although peripheral nerves can regenerate, clinical outcomes after peripheral nerve injuries are not always satisfactory, especially in cases of severe or proximal injuries. Further, autologous nerve grafting remains the gold standard for the reconstruction of peripheral nerves, although this method is still accompanied by issues of donor-site morbidity and limited supply. Cell therapy is a potential approach to overcome these issues. However, the optimal cell type for promoting axon regeneration remains unknown. Here, we report a novel experimental model dedicated to elucidation of the axon-promoting effects of candidate cell types using simple and standardized techniques. This model uses rat sciatic nerves and consists of a 25 mm-long acellular region and a crush site at each end. The acellular region was made by repeated freeze/thaw procedures with liquid nitrogen. Importantly, the new model does not require microsurgical procedures, which are technically demanding and greatly affect axon regeneration. To test the actual utility of this model, red fluorescent protein-expressing syngeneic Schwann cells (SCs), marrow stromal cells, or fibroblasts were grafted into the acellular area, followed by perfusion of the rat 2 weeks later. All types of grafted cells survived well. Quantification of regenerating axons demonstrated that SCs, but not the other cell types, promoted axon regeneration with minimum variability. Thus, this model is useful for differentiating the effects of various grafted cell types in axon regeneration. Interestingly, regardless of the grafted cell type, host SCs migrated into the acellular area, and the extent of axon regeneration was strongly correlated with the number of SCs. Moreover, all regenerating axons were closely associated with SCs. These findings suggest a critical role for SCs in peripheral nerve axon regeneration. Collectively, this novel experimental model is useful for elucidating the axon-promoting effects of grafted cells and for analyzing the biology of peripheral nerve axon regeneration.
Type: article
Appears in Collections:国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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