Graphene Oxide Substrate Promotes Neurotrophic Factor Secretion and Survival of Human Schwann-Like Adipose
Steffan H Llewellyn1,2, Alessandro Faroni1, Maria Iliut2
1Blond 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.
Abstract:
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.
