Chemical and Physical Priming of Human Mesenchymal Stem Cells to Alter Nonviral Gene Delivery Outcomes

Authors

Tyler KozisekFollow
Andrew Hamann, University of Nebraska-LincolnFollow
Amy Mantz, University of Nebraska-LincolnFollow
Mathias Schubert, University of Nebraska - LincolnFollow
Eva Schubert, University of Nebraska-LincolnFollow
Angela K. Pannier, University of Nebraska - LincolnFollow

Date of this Version

4-4-2017

Document Type

Article

Citation

Poster Session, University of Nebraska-Lincoln Research Fair, April 4-5, 2017

Comments

Copyright © 2017 Tyler Kozisek, Albert Nguyen, Andrew Hamann, Amy Mantz, Mathias Schubert, Eva Schubert, and Angela K. Pannier

Abstract

Human Mesenchymal Stem Cells: Human mesenchymal stem cells (hMSCs) are a multipotent cell, meaning they are able to differentiate into a more mature cell type, such as osteocytes, chondrocytes, and adipocytes, that are found in numerous tissues in the human body, such as bone marrow, fat, and muscle. Since hMSCs can be derived from adult human tissues, they do not have the same ethical concern associated with them as other stem cells, such as embryonic stem cells. Due to hMSCs multipotency and ease of obtaining, they have become one of the most widely researched stem cell types in areas such as tissue engineering and regenerative medicine, targeted delivery of drugs/secretion of therapeutic proteins, and cancer therapy.

Nonviral Gene Delivery: Nonviral gene delivery is the transfer of exogenous genetic material (e.g. plasmid DNA, siRNA) to cells using a nonviral vector, typically a cationic lipid or polymer. While nonviral delivery systems are considered safer than viral delivery systems, nonviral gene delivery suffers from low transfection efficiencies, especially in hMSCS, which limits its therapeutic potential. Our lab has previously shown that priming hMSCs with the glucocorticoid (GC) dexamethasone (DEX) 0-30 minutes prior to transfection can increase transgene expression by as much as 13 fold in hMSCs derived from numerous donors and tissues1.

Hypothesis: We hypothesize that physical and chemical priming of hMSCs prior to and during nonviral gene delivery can elicit a tailored response (i.e. activation of signaling pathways, increased proliferation, integrin clustering) that can alter the transfection outcomes in hMSCs.