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Cytotherapy. 2017 Oct;19(10):1208-1224. doi: 10.1016/j.jcyt.2017.07.009. Epub 2017 Aug 30.

Functional recovery upon human dental pulp stem cell transplantation in a diabetic neuropathy rat model.

Author information

1
Department of Biophysics, National Institute of Mental Health and Neurosciences, an Institute of National Importance, Bengaluru, Karnataka, India. Electronic address: indranidatta.nimhans@gmail.com.
2
Department of Pharmacology, Al-Ameen College of Pharmacy, Bengaluru, Karnataka, India.
3
Department of Biophysics, National Institute of Mental Health and Neurosciences, an Institute of National Importance, Bengaluru, Karnataka, India.
4
School of Regenerative Medicine, Manipal University, Bengaluru, Karnataka, India.

Abstract

Diabetic neuropathy (DN) is among the most debilitating complications of diabetes. Here, we investigated the effects of human dental pulp stem cell (DPSC) transplantation in Streptozotocin (STZ)-induced neuropathic rats. Six weeks after STZ injection, DPSCs were transplanted through two routes, intravenous (IV) or intramuscular (IM), in single or two repeat doses. Two weeks after transplantation, a significant improvement in hyperalgesia, grip-strength, motor coordination and nerve conduction velocity was observed in comparison with controls. A rapid improvement in neuropathic symptoms was observed for a single dose of DPSC IV; however, repeat dose of DPSC IV did not bring about added improvement. A single dose of DPSC IM showed steady improvement, and further recovery continued upon repeat IM administration. DPSC single dose IV showed greater improvement than DPSC single dose IM, but IM transplantation brought about better improvement in body weight. A marked reduction in tumor necrosis factor (TNF) α and C-reactive protein (CRP) levels was observed in the blood plasma for all treated groups, as compared with controls. With respect to inflammatory cytokines, repeat dose of DPSC IM showed further improvement, suggesting that a repeat dose is required to maintain the improved inflammatory state. Gene expression of inflammatory markers in liver confirmed amelioration in inflammation. Arachidonic acid level was unaffected by IV DPSC transplantation but showed noticeable increase through IM administration of a repeat dose. These results suggest that DPSC transplantation through both routes and dosage was beneficial for the retrieval of neuropathic parameters of DN; transplantation via the IM route with repeat dose was the most effective.

KEYWORDS:

C-reactive protein; dental pulp stem cells; diabetic neuropathy; hyperalgesia; inflammatory cytokines; intramuscular administration; nerve conduction velocity

PMID:
28864291
DOI:
10.1016/j.jcyt.2017.07.009
[Indexed for MEDLINE]

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