Glial-derived growth factor and pleiotrophin synergistically promote axonal regeneration in critical nerve injuries

Abstract

Nerve injuries due to trauma or tumor resection often result in long gaps that are challenging to repair. The best clinical option demands the use of autologous grafts that are associated with serious side effects. Bioengineered nerves are considered a good alternative, particularly if supplemented with growth factors, but current options do not match the regenerative capacity of autografts. This study revealed the synergistic effect of neurotrophins and pleiotrophins designed to achieve a broad cellular regenerative effect, and that GDNF-PTN are able to mediated axonal growth and partial functional recovery in a 4 cm nerve gap injury, albeit delays in remyelination. This report underscores the need for defining an optimal growth factor support for biosynthetic nerve implants.

LncRNA MIAT overexpression reduced neuron apoptosis in a neonatal rat model of hypoxic-ischemic injury through miR-211/GDNF

“…Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor that protects and repairs dopaminergic neurons, which has the potential ability to treat Parkinson's disease [9,10]. GDNF can also promote axonal regeneration in critical nerve injury and inhibit spinal microglia activation to relieve age-related neuromuscular dysfunction [11,12]. Decrease of GDNF contributed to the learning and cognitive disorders in neonatal rats [13].…”

Restoration of Neurological Function Following Peripheral Nerve Trauma

“…Two to three days after a crush nerve injury, the severed axons begin to regenerate into the distal part of the nerve and continue to regenerate until they reach and reinnervate their original targets. Axon regeneration is promoted by the denervated Schwann cells in the distal portion of the nerve by their release of neurotrophic factors, and their extracellular matrix [15][16][17][18][19][20][21]. The greater the number of axons that regenerate through the distal nerve, the greater the extent of neurological recovery [19,22] Generally, the precision of target reinnervation is extremely high [19].…”

“…The primary drawback to using lengths of nerve as a graft is that their use requires sacrificing the function of that nerve. This creates a permanent neurological deficit [15,46,47].…”

“…The efficacy of collagen conduits is increased when they contain, or release, neurotrophic or other factors, such as GDNF [180] or neurotrophin-3 (NT-3) [182]. Alginate/chitosan conduits induce more extensive axon regeneration when they contain or release simvastatin [183], NGF [184][185][186][187], GDNF [184], VEGF [188], GDNF and NGF [24,189], or pleiotrophin [15]. Efficacy is also increased when alginate/chitosan conduits are combined with fibronectin, laminin [190], or when hydrogel conduits contain Matrigel, collagen, heparin (sulfate), laminin, or fibronectin [190].…”

Biomimetic Approaches for Separated Regeneration of Sensory and Motor Fibers in Amputee People: Necessary Conditions for Functional Integration of Sensory–Motor Prostheses With the Peripheral Nerves

“…The gold standard are autografts, although they have several associated side effects, such as secondary surgery, donor site morbidity, size mismatch, and limited tissue availability. Commercial allografts, such as Avance R Nerve Graft (Axogen, Inc., FL, United States), which consists of the ECM of a human nerve, without cellular or non-cellular [Grosheva et al, 2016] 130 pg/mL [Shakhbazau et al, 2012] 0.8-1 µg/mL [Kemp et al, 2011;Santos et al, 2016a] 0.5 µg/mL [Chang et al, 2017;Li et al, 2018] 1 µg/mL [Kemp et al, 2011;Santos et al, 2016a] 20 µg/mL [Anand et al, 2017] BDNF 5 pg/mg [Grosheva et al, 2016] 14.8 pg/mL [Omura et al, 2005;Shakhbazau et al, 2012;Shakhbazau et al, 2012] 10 µg/mL [Kemp et al, 2011;Santos et al, 2016a] 10-100 µg/mL [Chang et al, 2017] 2 µg/mL [Kemp et al, 2011;Santos et al, 2016a] 20 µg/mL [Anand et al, 2017] NT3 6 pg/mL [Shakhbazau et al, 2012] 100 pg/mg [Omura et al, 2005;Shakhbazau et al, 2012] 2 µg/mL [Kemp et al, 2011;Santos et al, 2016a] 1 µg/mL [Glazner et al, 1993] 0.5 µg/mL [Sterne et al, 1997] GDNF 150 pg/mL [Shakhbazau et al, 2012] 20 µg/mL [Alsmadi et al, 2018] 20 µg/mL [Anand et al, 2017] 20 µg/mL [Anand et al, 2017] IGF1 793 pg/mg [Grosheva et al, 2016] 50-100 µg/mL [Sullivan et al, 2008] 100 µg/mL [Apel et al, 2010] 100 µg/mL [Apel e...…”