Nerve growth factor gene therapy improves bone marrow sensory innervation and nociceptor-mediated stem cell release in a mouse model of type 1 diabetes with limb ischaemia

• DOI: 10.1007/s00125-019-4860-y
• Publication Date: 2019-04-24T05:38:10Z
• Authors: Zexu Dang; Elisa Avolio; Ambra Albertario; Graciela B. Sala-...; Anita C. Thomas; Nianhong Wang; Costanza Emanueli; Paolo Madeddu
• Keywords: Diabetic Neuropathy; Stem Cell Therapy

Sensory neuropathy is common in people with diabetes; can also affect the bone marrow of individuals type 2 diabetes. However, no information exists on state sensory innervation 1 neurons are trophically dependent nerve growth factor (NGF) for their survival. The aim this investigation was twofold: (1) to determine if affects a mouse model diabetes, consequences stem cell liberation after tissue injury; and (2) verify single systemic injection NGF gene exerts long-term beneficial effects these phenomena.A diabetes generated CD1 mice by administration streptozotocin; vehicle administered non-diabetic control animals. Diabetic animals were randomised receive therapy either human or β-galactosidase. After 13 weeks, limb ischaemia induced both groups study recovery post injury. When killed, samples peripheral blood taken assess mobilisation homing, levels substance P muscle vascularisation. An vitro cellular adopted signalling downstream related neurotrophic pro-apoptotic effects. Normally distributed variables compared between using unpaired Student's t test non-normally assessed Wilcoxon-Mann-Whitney test. Fisher's exact employed categorical variables.Immunohistochemistry indicated 3.3-fold reduction number P-positive nociceptive fibres diabetic (p < 0.001 vs non-diabetic). Moreover, abrogated creation neurokinin gradient which, mice, favoured homing bone-marrow-derived cells expressing receptor (NK1R). Pre-emptive prevented denervation, contrasting inhibitory effect NK1R-expressing cells, restored flow from ischaemia. In hNGF neurite outgrowth exerted anti-apoptotic actions rat PC12 exposed high glucose via activation canonical tyrosine kinase (TrkA) pathway.This shows, first time, occurrence which translates into an altered modulation depressed release P-responsive following improves innervation, benefits healing Nociceptors may represent new target treatment ischaemic complications