Blond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PL, UK.
Department of Materials and National Graphene Institute, The University of Manchester, Manchester, M13 9PL, UK.
Adv Biol (Weinh). 2021 Apr;5(4):e2000271. doi: 10.1002/adbi.202000271. Epub 2021 Mar 4.
Mesenchymal stromal cells from adipose tissue (AD-MSCs) exhibit favorable clinical traits for autologous transplantation and can develop 'Schwann-like' phenotypes (sAD-MSCs) to improve peripheral nerve regeneration, where severe injuries yield insufficient recovery. However, sAD-MSCs regress without biochemical stimulation and detach from conduits under unfavorable transplant conditions, negating their paracrine effects. Graphene-derived materials support AD-MSC attachment, regulating cell adhesion and function through physiochemistry and topography. Graphene oxide (GO) is a suitable substrate for human sAD-MSCs incubation toward severe peripheral nerve injuries by evaluating transcriptome changes, neurotrophic factor expression over a 7-days period, and cell viability in apoptotic conditions is reported. Transcriptome changes from GO incubation across four patients are minor compared to biological variance. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF) gene expression is unchanged from sAD-MSCs on GO substrates, but NGF and GDNF protein secretion increase at day 3 and 7. Secretome changes do not improve dorsal root ganglia neuron axon regeneration in conditioned media culture models. Fewer sAD-MSCs detach from GO substrates compared to glass following phosphate buffer saline exposure, which simulates apoptotic conditions. Overall, GO substrates are compatible with sAD-MSC primed for peripheral nerve regeneration strategies and protect the cell population in harsh environments.
脂肪组织来源的间充质基质细胞(AD-MSCs)表现出有利于自体移植的临床特征,并且可以发展出“许旺样”表型(sAD-MSCs),以改善周围神经再生,在严重损伤的情况下,恢复效果不佳。然而,sAD-MSCs 在没有生化刺激的情况下会退化,并在不利的移植条件下从导管上脱落,从而消除了其旁分泌作用。石墨烯衍生材料支持 AD-MSC 的附着,通过物理化学和形貌来调节细胞的黏附和功能。氧化石墨烯(GO)是一种适合人类 sAD-MSCs 孵育的底物,通过评估转录组变化、7 天内神经营养因子表达以及细胞在凋亡条件下的活力,来评估其对严重周围神经损伤的作用。与生物学变异性相比,来自 GO 孵育的四个患者的转录组变化较小。GO 底物上的 sAD-MSCs 神经生长因子(NGF)、脑源性神经营养因子(BDNF)和胶质源性神经营养因子(GDNF)基因表达不变,但 NGF 和 GDNF 蛋白分泌在第 3 天和第 7 天增加。分泌组变化并不能改善条件培养基培养模型中背根神经节神经元轴突的再生。与玻璃相比,GO 底物上的 sAD-MSCs 在磷酸盐缓冲盐水暴露后(模拟凋亡条件)从 GO 底物上脱落的细胞更少。总的来说,GO 底物与为周围神经再生策略而预先激活的 sAD-MSC 兼容,并在恶劣环境中保护细胞群体。