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

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.

Implantation of a nerve protector embedded with human GMSC-derived Schwann-like cells accelerates regeneration of crush-injured rat sciatic nerves

“…[ 33 , 49 ]. In recent years, various approaches have been developed to promote induction of MSCs into Schwann-like cells, particularly the use of certain small molecules or growth factors [ 48 , 50 ] and engineered substrates or scaffolds such as graphene oxide substrate [ 51 ], 3D-printed polycaprolactone/polypyrrole (PCL/PPy) conductive scaffold [ 52 ], 3D-printed bionic polycaprolactone (PCL) polymer scaffold [ 53 ], and aligned nanofibers [ 54 ]. Consistent with our recent studies [ 37 ], we, herein, have also demonstrated that GMSCs could directly and rapidly convert into Schwann-like cells when they were encapsulated in methacrylated 3D-collagen hydrogel and cultured under the regular MSC culture medium without the additional introduction of special nutritional and growth factor supplements (Fig.…”

Preconditioning of MSCs for Acute Neurological Conditions: From Cellular to Functional Impact—A Systematic Review

“…Furthermore, when cultured in 5% oxygen, the levels of GDNF, BDNF, EGF, IL-1β, and IL-6 increased while the levels of VEGF-A, bFGF, and TGF-β1 decreased [24]. The increased release of growth factors (NGF and GDNF) also occurred with the use of graphene oxide scaffolds, supporting AD-MSCs attachment and regulating cell adhesion and function [23].…”

“…Culture Scaffolds/3D Culture/Biomechanical Forces Tissue engineering led to the development of scaffolds and 3D cultures, and these are now widely used to culture MSCs. Three studies evaluated the use of different systems to carry out preconditioning, microfluidic devices [10], encapsulation of MSCs in hydrogel scaffolds [24], and graphene oxide-substrate [23]).…”

Graphene-Oxide-Enriched Biomaterials: A Focus on Osteo and Chondroinductive Properties and Immunomodulation

“…GO is also an applicable substrate in the presence of mesenchymal stromal cells from adipose tissue. It has been employed for enhancing peripheral nerve regeneration, demonstrating good biocompatibility and protection from the surrounding context, and furthermore improving nerve growth factor and glial-derived neurotrophic factor protein secretion [ 25 ].…”