Dental pulp-derived stem cells can counterbalance peripheral nerve injury-induced oxidative stress and supraspinal neuro-inflammation in rat brain

Abstract

Previously, we reported the successful regeneration of injured peripheral nerves using human dental pulp stem cells (DPSCs) or differentiated neuronal cells from DPSCs (DF-DPSCs) in a rat model. Here, we attempted to evaluate oxidative stress and supraspinal neuro-inflammation in rat brain after sciatic nerve injury (SNI). We divided our experimental animals into three SNI groups based on time. The expression of a microglial (Iba1) marker and reactive oxygen species (ROS) was lower in DPSCs and higher in DF-DPSCs. In contrast, the expression of an astroglial (GFAP) marker was higher in DPSCs and lower in DF-DPSCs at 2 weeks. However, the expression of ROS, Iba1 and GFAP gradually decreased at 8 and 12 weeks in the SNI DPSCs and DF-DPSCs groups compared to the SNI control. Furthermore, anti-inflammatory cytokine (IL-4 and TGF-β) expression was lower at 2 weeks, while it gradually increased at 8 and 12 weeks after surgery in the SNI DPSCs and DF-DPSCs groups. Similarly, SNI DPSCs had a high expression of pAMPK, SIRT1 and NFkB at the onset of SNI. However, 12 weeks after surgery, pAMPK and SIRT1 expression levels were higher and NFkB was down-regulated in both DPSCs and DF-DPSCs compared to the control group. Finally, we concluded that DPSCs responded early and more efficiently than DF-DPSCs to counterbalance peripheral nerve injury (PNI)-induced oxidative stress and supraspinal neuro-inflammation in rat brain.

Epigenetic Regulation of Dental Pulp Stem Cell Fate

“…Moreover, DPSCs in prevascularized, scaffold-free, microtissue spheroids can successfully regenerate vascular dental pulp-like tissue, which provides a new strategy for endodontic treatment and makes dentin-pulp regeneration possible [ 85 ]. The clinical application potential of DPSCs is not only in dentistry but also in treatments for other diseases, such as craniofacial bone defects [ 86 ], muscle regeneration [ 87 ], myocardial infarction [ 88 ], Alzheimer's disease [ 89 ], nervous system injuries [ 90 ], Parkinson's disease, diabetes [ 91 ], stress urinary incontinence [ 80 ], osteoarthritis [ 92 ], and liver diseases [ 93 ].…”

Effects of Resistance Training and Bowdichia virgilioides Hydroethanolic Extract on Oxidative Stress Markers in Rats Submitted to Peripheral Nerve Injury

“…In addition to OS in the organ innervated by the injured nerve, PNI promotes the release of certain inflammatory mediators and ERs into the plasma and the dorsal root ganglia, which in turn ascend to the brain. Surprisingly, little attention is paid to the central nervous response [ 64 ]. OS in neural tissues causes signaling and interrupted homeostasis and is responsible for numerous events ranging from the protein catabolism to neuronal death.…”

“…OS in neural tissues causes signaling and interrupted homeostasis and is responsible for numerous events ranging from the protein catabolism to neuronal death. Higher levels of reactive species expression also activate nuclear factor kappa B, which in turn initiates the transcription of pro-inflammatory mediators in the central nervous system [ 64 , 65 ].…”

Stem‐cell–based therapies to enhance peripheral nerve regeneration

“…These cells also demonstrated myelinating capacity and improved functional recovery from rodent sciatic nerve transection . They have been shown to counterbalance peripheral nerve injury–induced oxidative stress and neuroinflammation . Interestingly, these cells may have their regenerative effects seen in crush injury enhanced by application of an external pulsed electromagnetic field .…”

“…105 They have been shown to counterbalance peripheral nerve injury-induced oxidative stress and neuroinflammation. 106 Interestingly, these cells may have their regenerative effects seen in crush injury enhanced by application of an external pulsed electromagnetic field. 107 Clinically, wisdom teeth may one day be a potential source of autologous donation for this particular type of stem cell for use in the treatment of peripheral nerve injuries.…”