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Graphene Oxide Substrate Promotes Neurotrophic Factor Secretion and Survival of Human Schwann-Like Adipose Mesenchymal Stromal Cells

Year: 2021

Journal: Adv. Biol., Volume 5, APR

Authors: Llewellyn, Steffan H.; Faroni, Alessandro; Iliut, Maria; Bartlam, Cian; Vijayaraghavan, Aravind; Reid, Adam J.

Organizations: Engineering and Physical Science Research Council (EPSRC) [EP/L01548X/1]; Graphene NOWNANO Centre for Doctoral Training; Hargreaves and Ball Trust; Academy of Medical Sciences [AMS-SGCL7]; Rosetrees Trust; Stoneygate Trust [M746]

Keywords: adipose stem cells; graphene oxide; nerve regeneration; peripheral nerve injuries; Schwann cells

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.