Methods for drug discovery using stem cell-derived schwann cells
a technology of drug discovery, which is applied in the field of drug discovery using stem cell-derived schwann cells, can solve the problems of increased morbidity and mortality, no effective treatment of dpn, and reduced quality of li
Patent Information
- Authority / Receiving Office
- US · United States
- Patent Type
- Applications(United States)
- Current Assignee / Owner
- Publication Date
- 2019-10-31
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Abstract
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Continuation of International Patent Application No. PCT / US17 / 61549 filed Nov. 14, 2017, which claims priority to U.S. Application No. 62 / 421,816 filed Nov. 14, 2016, and the contents of each of which are hereby incorporated by reference in their entireties herein, and to each of which priority is claimed.INTRODUCTION
[0002] The presently disclosed subject matter relates to use of Schwann cell precursors and Schwann cells derived from stem cells (e.g., human stem cells) for drug discovery in regeneration of peripheral nervous system (PNS) and / or central nervous system (CNS), prevention and / or repair of myelin damages, and / or prevention and / or treatment of Schwann cell-related disorder (e.g., peripheral neuropathy diabetic peripheral neuropathy). It further provides for methods of treatment of Schwann cell related disorders using compounds identified by said drug discovery materials and methods.BACKGROUND
[0003] Schwann c...
Examples
example 1
SUMMARY
[0214]Schwann cell precursors and Schwann Cells were derived from human stem cells (e.g., hPSC). The inventors established an hESC-based in vitro model of DPN that revealed the selective vulnerability of human SCs to hyperglycemia-induced cytotoxicity and activation of the polyol pathway. The inventors further used this model to perform high throughput drug screening and identified Bupropion as a compound for treatment of DPN. Bupropion can counteract the high-glucose induced cytotoxicity in SCs in vitro and rescues the neuropathy related histological and behavioral deficits in STZ-treated diabetic mice.
Methods and Materials
[0215]Culture of Undifferentiated Human Embryonic Stem Cells (hESCs)
[0216]hESC line H9 (WA-09) and derivatives (SOX10::GFP; SYN::ChR2-YFP; SYN::YFP;PHOX2B:GFP; EF1::RFP EDNRB− / −) as well as 2 independent hiPSC lines (healthy and Familial Dysautonomia, Sendai-based, OMSK (Cytotune)) were maintained on mouse embryonic fibroblasts (MEF, Global Stem, Rockville...