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MSc Human Biology Thesis Defence - Shahreen Rahman

Posting Date(s)
Date
Location
Web Conference

Presenter: Shahreen Rahman

Title:  Investigating the function of the Schwann cells in impaired diabetic wound healing 

Abstract:

Type-2 Diabetes Mellitus (T2DM) is a multifactorial disorder that occurs due to a lack of insulin and hyperglycemia. In this work, we related the two major complications of T2DM: wound healing defects and diabetic peripheral neuropathy in the skin. Cutaneous nerves extend throughout the dermis and epidermis and control both the functional and reparative capacity of the skin. Nerve axons are reduced in the skin of a diabetic and further decrease in wounds. From previous work, our lab demonstrated as apposed to the nerve axons, the associated Schwann cells located around the wound are important to undergo an extensive reprogramming process and migrate towards the wound bed releasing bioactive molecules, which contribute to wound closure. However, their role is still unknown in diabetic wound healing. The purpose of this study was to evaluate the presence and contribution of Schwann cells in cutaneous wounds following an injury and observe the effectiveness of Oncostatin M to rescue diabetic wounds. Methods: To investigate this, we have used the diabetic rodent model— genetically modified Db/Db diabetic mice (n=5) lacking leptin receptors. A 6mm punch biopsy wound is induced in the back skin, and healing is tracked for 5, 10, 15, and 21 days. As days 10 and 15 showed the most significant changes, we performed the immunofluorescent analysis of S100B & P75NTR and neurofilaments will determine the numbers of Schwann cells and axons to examine the interventions. The immunohistochemistry was performed to understand the mechanism of Oncostatin-M, a pleiotropic, IL-6 family member that is released from Schwann cells (SCs)to rescue the diabetic wound as an experimental therapy. Results: Immunofluorescence staining showed 85.28% reduction in S100β positive and 80.14% reduction in p75NTR positive Schwann cell markers on day 10 as well as 72.35% S100β positive cells and 65.28% p75NTR positive cells still reduced at day 15 indicating a significant (p≤0.05) percentage reduction of Schwann cells number in the dermis of diabetic skin wounds and healing is delayed while the control wounds returned to baseline by day 15 post-injury. The rescue treatment with Oncostatin-M contributed to the healing progression of the diabetic wound compared to vehicle treatment increased proliferation of epidermal cells to 61% and angiogenesis to 28.67% than the vehicle-treated wound. Conclusion: The outcome of this study could pave the path for novel therapeutic intervention for diabetic wound healing and could be a potential clinical trial to explore the possibility of accelerating wound healing to rescue peripheral vascular disease and other chronic wound-induced limb amputation. 

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