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Neurogenic Stroma Reprograming using Tissue Nanotransfection (TNT) to Rescues Diabetic Peripheral Neuropathy
Subhadip Ghatak, Sayak Bhattacharya, Jyothi Nalluri Naga, Subendu Sarkar, Puneet Khandelwal, Sashwati Roy, Chandan K Sen and Savita Khanna
University
2019-02-15
Presenter: Savita Khanna
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal.
Director Name: savita khanna
Author Category: Other Specialty Resident
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
TNT is a non-viral nanotechnology-based platform that may deliver ABM (Ascl1, Brn2, and Myt1l) and induce neurogenic reprograming of murine skin in vivo (Nat Nano 2018). Induced neural cells (iN) develop in the skin and acquire functional electrophysiological properties. In this work we report that TNT-ABM, in addition to reprograming skin cells to iN, reprograms the skin stroma such that the resulting neurotrophic environment support development of iN in the skin. The objective of this work was to apply TNT towards rescuing cutaneous nerve fibers from diabetic peripheral neuropathy (DPN). In DPN, neurotrophin signaling mechanisms become dysfunctional, particularly in regard to nerve growth factor (NGF). Increasing the level of NGF within the skin has the potential to create a more neurotrophic environment that sustains nerve fiber density throughout the progression of DPN. Nanoelectroporation mediated transfection of mouse embryonic fibroblasts (MEF) with ABM caused reprogramming into induced neurons and increases NGF expression in vitro. TNT- ABM converted skin cells in C57Bl/6 mice into induced neurons. Along with this cell conversion, we observed significant increase in NGF expression in ABM transfected skin in both C57Bl6 and db/db mice. Following, TNT-ABM of the hindlimb of db/db mice, intraepidermal never fiber density (PGP9.5 positive nerve fibers), was higher indicating a possible rescue from diabetes-dependent loss of fiber density. In summary, the current state of evidence points towards the possibility that topical TNT-ABM, a 0.1 sec procedure, of skin may induce a neurotrophic response that can be leveraged to rescue peripheral diabetic neuropathy. neuropathy.
