May Zacnicte, Torres-Espín Abel, Lucas-Osma Ana M, Batty Nicholas J, Raposo Pamela, Fenrich Keith K, Stykel Morgan G, Führmann Tobias, Shoichet Molly, Biernaskie Jeff, Fouad Karim
Department of Physical Therapy, Faculty of Rehabilitation Medicine, and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB Canada.
Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB Canada.
Neurosci Lett. 2017 Sep 29;658:67-72. doi: 10.1016/j.neulet.2017.08.045. Epub 2017 Aug 24.
A major goal of Schwann cell (SC) transplantation for spinal cord injury (SCI) is to fill the injury site to create a bridge for regenerating axons. However, transplantation of peripheral nerve SCs requires an invasive biopsy, which may result in nerve damage and donor site morbidity. SCs derived from multipotent stem cells found in skin dermis (SKP-SCs) are a promising alternative. Regardless of source, loss of grafted SCs post-grafting is an issue in studies of regeneration, with survival rates ranging from ∼1 to 20% after ≥6 weeks in rodent models of SCI. Immune rejection has been implicated in these low survival rates. Therefore, our aim was to explore the role of the immune response on grafted SKP-SC survival in Fischer rats with a spinal hemisection injury. We compared SKP-SC survival 6 weeks post-transplantation in: (I) cyclosporine-immunosuppressed rats (n=8), (II) immunocompetent rats (n=9), and (III) rats of a different sub-strain than the SKP-SC donor rats (n=7). SKP-SC survival was similar in all groups, suggesting immune rejection was not a main factor in SKP-SC loss observed in this study. SKP-SCs were consistently found on laminin expressed at the injury site, indicating detachment-mediated apoptosis (i.e., anoikis) might play a major role in grafted cell loss.
施万细胞（SC）移植治疗脊髓损伤（SCI）的一个主要目标是填充损伤部位，为再生轴突搭建桥梁。然而，外周神经施万细胞的移植需要进行侵入性活检，这可能导致神经损伤和供体部位发病。源自皮肤真皮层中多能干细胞的施万细胞（SKP-SC）是一种有前景的替代方案。无论来源如何，移植后移植的施万细胞丢失都是再生研究中的一个问题，在SCI啮齿动物模型中，≥6周后存活率在1%至20%之间。免疫排斥被认为与这些低存活率有关。因此，我们的目的是探讨免疫反应对脊髓半横断损伤的Fischer大鼠移植的SKP-SC存活的作用。我们比较了移植后6周时SKP-SC在以下三组中的存活率：（I）环孢素免疫抑制大鼠（n = 8），（II）免疫活性大鼠（n = 9），以及（III）与SKP-SC供体大鼠不同亚系的大鼠（n = 7）。所有组中SKP-SC的存活率相似，表明免疫排斥不是本研究中观察到的SKP-SC丢失的主要因素。在损伤部位表达的层粘连蛋白上始终能发现SKP-SC，这表明脱离介导的细胞凋亡（即失巢凋亡）可能在移植细胞丢失中起主要作用。
